A Study Of Oral Palbociclib (PD-0332991), A CDK4/6 Inhibitor, As Single Agent In Japanese Patients With Advanced Solid Tumors Or In Combination With Letrozole For The First-Line Treatment Of Postmenopausal Japanese Patients With ER (+) HER2 (-) Advanced Breast Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01684215
• Collaborator: (none)
• Enrollment: 61
• Locations: 16
• Arms: 3
• Actual Duration (Months): 72.2
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This study is comprised of two portions: a Phase 1 portion and a Phase 2 portion. The Phase 1 portion is a single-country, non-randomized, open label, clinical trial which will evaluate the safety, tolerability, preliminary efficacy, and PK profile of PD-0332991 as a single agent in Japanese patients with advanced solid tumors, and PD-0332991 in combination with letrozole in the first-line treatment of Japanese patients with ER(+) HER2(-) ABC. The Phase 2 portion is a single-country, non-randomized, open-label, single-cohort, multi-center clinical trial to evaluate the efficacy and safety of PD-0332991 in combination with letrozole for the first-line treatment of postmenopausal Japanese patients with ER(+) HER2(-) ABC.

Condition or Disease	Intervention/Treatment	Phase
Neoplasms; Breast Neoplasms	Drug: PD-0332991; Drug: PD-0332991; Drug: letrozole; Drug: PD-0332991; Drug: letrozole	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: Non-Randomized
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A PHASE 1/2 STUDY OF THE EFFICACY, SAFETY, AND PHARMACOKINETICS OF ORAL PD-0332991, A CYCLIN-DEPENDENT KINASE 4 AND 6 (CDK4/6) INHIBITOR, AS SINGLE AGENT IN JAPANESE PATIENTS WITH ADVANCED SOLID TUMORS OR IN COMBINATION WITH LETROZOLE FOR THE FIRST-LINE TREATMENT OF POSTMENOPAUSAL JAPANESE PATIENTS WITH ER (+) HER2 (-) ADVANCED BREAST CANCER
• Actual Study Start Date: Oct 19, 2012
• Actual Primary Completion Date: Mar 4, 2016
• Actual Study Completion Date: Oct 25, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single-agent PD-0332991 Phase 1 Part 1	Drug: PD-0332991; PD-0332991 (100 mg or 125 mg) will be orally administered once a day for 3 weeks followed by 1 week off treatment, in the morning on an empty stomach. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.
Experimental: PD-0332991 in combination with letrozole Phase 1 Part 2	Drug: PD-0332991; PD-0332991, 125 mg, will be orally administered with food once a day for 3 weeks followed by 1 week off treatment. PD-0332991 will be administered once a day together with letrozole. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.; Drug: letrozole; Letrozole, 2.5 mg, will be orally administered once a day in continuous daily dosing together with PD-0332991. Dose reduction of letrozole is not permitted, but dosing interruptions for letrozole-related toxicity are allowed as per investigator's medical judgement.
Experimental: PD-0332991 with letrozole Phase 2	Drug: PD-0332991; PD-0332991, 125 mg, will be orally administered with food once a day for 3 weeks followed by 1 week off treatment. PD-0332991 will be administered once a day together with letrozole. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.; Drug: letrozole; Letrozole, 2.5 mg, will be orally administered once a day in continuous daily dosing together with PD-0332991. Dose reduction of letrozole is not permitted, but dosing interruptions for letrozole-related toxicity are allowed as per investigator's medical judgement.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose Limiting Toxicities (DLT): Part 1 Phase 1 [Lead-in period (Day -7) up to Day 28 (Cycle 1)]

   DLT was classified as per common terminology criteria for adverse events (CTCAE) version 4.0 as any of the events occurring during 28 days of Cycle 1,attributed to study drug:grade 4 neutropenia(for a duration of greater than [>]7 days); febrile neutropenia (grade greater than or equal to [>=]3 neutropenia,body temperature >=38.5 degree Celsius);grade >=3 thrombocytopenia with bleeding episode;grade 4 thrombocytopenia;grade >=3 non-hematologic toxicity except grade 3 or more nausea, vomiting,electrolyte abnormality(if controllable by therapy);grade 3 QTc prolongation(>500 millisecond [msec])persist after correction of reversible cause such as electrolyte abnormalities or hypoxia. Lack of hematologic recovery (platelets less than [<]50,000/microliter [mcL],absolute neutrophil count <1,000/mcL,hemoglobin <8.0 gram/deciliter [g/dL]) or prolonged non hematologic toxicities that delays initiation of next dose by >7 days;receipt of <75 percent of planned dose in first cycle due to toxicity.

2. Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 Phase 1 [Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days)]

   A treatment related AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Relatedness was judged by investigator. AEs included both serious and non-serious adverse events.

3. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) By Severity: Part 2 Phase 1 [Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days)]

   AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment but increased in National Cancer Institute (NCI) CTCAE grade during study treatment period. AE severity was defined to be the maximum toxicity grade of the TEAEs experienced by the participants during the study. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).

4. Percentage of Participants With 1 Year Progression Free Survival (PFS): Phase 2 [From initiation of treatment up to 12 months]

   PFS was defined as the time from first dose of study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurred first. PD was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.1-year PFS was defined as the percentage of participants without PFS events (PD or death due to any cause) at 12 months based on the Kaplan-Meier estimate. Percentage of participants with 1-year PFS with 90% confidence interval (CI) were reported.

Secondary Outcome Measures

1. Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Phase 1 (Part 1) and Phase 2 [Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (up to 308 days), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1526 days)]

   A treatment related AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Relatedness was judged by investigator. AEs included both serious and non-serious adverse events.

2. Number of Participants With Treatment-Emergent Adverse Events (AEs) By Severity: Phase 1 (Part 1) and Phase 2 [Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (up to 308 days), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1526 days)]

   AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment but increased in NCI CTCAE version 4.0 grade during study treatment period. AE severity was defined to be the maximum toxicity grade of the TEAEs experienced by the participants during the study. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).

3. Number of Participants With Clinically Significant Laboratory Abnormalities [Part 1 Phase 1: Lead-in period (Day -7) up to 308 days; Part 2 Phase 1: Baseline (Day 1) up to 1673 days; Phase 2: Baseline (Day 1) up to 1526 days]

   Abnormality criteria: hemoglobin: <0.8*lower limit of normal [LLN], platelets: <0.5*LLN or >1.75*upper limit of normal [ULN], leukocytes: <0.6*LLN or >1.5*ULN, lymphocytes, total neutrophils: <0.8*LLN or >1.2*ULN, basophils, eosinophil,monocytes: >1.2*ULN); aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase (GT): >0.3*ULN, total protein, albumin: <0.8*LLN or >1.2*ULN, total bilirubin, direct bilirubin: >1.5*ULN; blood urea nitrogen, creatinine: >1.3*ULN, uric acid: >1.2*ULN; sodium: <0.95*LLN or >1.05*ULN, potassium, chloride, calcium, magnesium: <0.9*LLN or >1.1*ULN, phosphate: <0.8*LLN or >1.2*ULN; creatine kinase: >2.0*ULN, glucose fasting: <0.6*LLN or >1.5*ULN, glycosylated haemoglobin: >1.3*ULN;urinalysis dipstick (urine protein, urine blood >=1); urine protein 24 hour: >1.1*ULN; coagulation Activated partial thromboplastin time [APTT], Prothrombin, prothrombin international ratio: >1.1*ULN.

4. Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 [Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8]

   AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.

5. AUCtau Dose Normalized to 125 Milligram (mg) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 [Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8]

   AUCtau Dose Normalized to 125 mg is area under the plasma concentration-time curve over dosing interval dose normalized to 125 mg which is calculated by log-linear trapezoidal method.

6. Area Under the Plasma Concentration-Time Curve From 0 to Time 24 Hours (AUC24) of PD-0332991 Following Single Dose: Part 1 Phase 1 [Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12 and 24 hours post-dose in Lead-in period (Day -7)]

   AUC24 is area under the plasma concentration-time curve from 0 to time 24 hours which is calculated by log-linear trapezoidal method.

7. AUC24 Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1 [Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12 and 24 hours post-dose in Lead-in period (Day -7)]

   AUC24 Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to time 24 hours dose normalized to 125 mg which is calculated by log-linear trapezoidal method.

8. Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of PD-0332991 Following Single Dose: Part 1 Phase 1 [Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)]

   AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.

9. AUCinf Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1 [Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)]

   AUCinf Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to infinity dose normalized to 125 mg which is calculated by log-linear trapezoidal method.

10. Area Under the Plasma Concentration-Time Curve From 0 to Time of Last Measurable Concentration (AUClast) of PD-0332991 Following Single Dose: Part 1 Phase 1 [Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)]

    AUClast is area under the plasma concentration-time curve from 0 to time of last measurable concentration which is calculated by log-linear trapezoidal method.

11. AUClast Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1 [Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)]

    AUClast Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to time of last measurable concentration dose normalized to 125 mg which is calculated by log-linear trapezoidal method.

12. Apparent Oral Clearance of PD-0332991: Part 1 Phase 1 [Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8]

    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by AUCinf. AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.

13. Maximum Observed Plasma Concentration (Cmax) Of PD-0332991: Part 1 Phase 1 [Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8]

    Cmax is maximum plasma concentration which is observed directly from the actual time-concentration data.

14. Cmax Dose Normalized to 125 mg of PD-0332991: Part 1 Phase 1 [Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8]

    Cmax Dose Normalized to 125 mg is maximum plasma concentration dose normalized to 125 mg which is observed directly from the actual time-concentration data.

15. Pre-dose Plasma Concentration (Ctrough) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 [Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8]

    Ctrough is pre-dose concentration during multiple dosing which is observed directly from the actual time-concentration data.

16. Accumulation Ratio (Rac) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 [Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8]

    Rac is the ratio of AUCtau (after multiple doses) to AUCtau (after single dose). AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.

17. Linearity (Rss) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 [Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8]

    Rss is the ratio of AUCtau (after multiple doses) to AUCinf (after single dose). AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method. AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.

18. Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991: Part 1 Phase 1 [Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8]

    Tmax is time at which maximum plasma concentration (Cmax) was observed. It was observed directly from data as time of first occurrence.

19. Terminal Half-Life (t1/2) of PD-0332991: Part 1 Phase 1 [Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8]

    t1/2 is terminal elimination half-life which is calculated by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

20. Volume of Distribution (Vz/F) of PD-0332991 Following Single Dose: Part 1 Phase 1 [Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)]

    Vz/F is apparent volume of distribution estimated from terminal phase, which is calculated as CL/F/kel. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method (AUCinf). kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

21. Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991: Phase 2 [0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15]

    AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.

22. Apparent Oral Clearance of PD-0332991: Phase 2 [0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15]

    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by AUCtau. AUCtau is the area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.

23. Maximum Observed Plasma Concentration (Cmax) Of PD-0332991: Phase 2 [0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15]

    Cmax is maximum plasma concentration which is observed directly from the actual time-concentration data.

24. Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991: Phase 2 [0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15]

    Tmax is time at which maximum plasma concentration (Cmax) was observed. It was observed directly from data as time of first occurrence.

25. Pre-dose Plasma Concentration (Ctrough) of PD-0332991: Phase 2 [0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15]

    Ctrough is pre-dose concentration during multiple dosing which is observed directly from the actual time-concentration data.

26. Percentage of Participants With Objective Response: Phase 1 [From initiation of treatment up to disease progression (up to 30 months)]

    Objective response (OR) was defined as a complete response (CR) or partial response (PR) according to the RECIST version 1.1 recorded from first dose of study treatment until disease progression or death due to any cause. CR was defined as disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis <10 millimeter [mm]). PR was defined as a >=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Percentage of participants with objective response (who achieved CR or PR) were reported.

27. Percentage of Participants With Objective Response: Phase 2 [From initiation of treatment up to disease progression (up to 1526 days)]

    Objective response was defined as a complete response (CR) or partial response (PR) according to the RECIST version 1.1 recorded from first dose of study treatment until disease progression or death due to any cause. PD was defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. CR was defined as disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis <10 mm). PR was defined as a >=30% decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Percentage of participants with objective response (who achieved CR or PR) were reported.

28. Duration of Response (DOR): Part 2 Phase 1 [baseline up to 1673 days]

    Duration of response was defined as the interval from the first documentation of objective tumor response in participants with CR (disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis <10 millimeter [mm]) or PR (a >=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions) according to RECIST version 1.1 to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first.

29. Duration of Response (DOR): Phase 2 [From initiation of treatment up to disease progression (up to 1526 days)]

    Duration of response was defined as the interval from the first documentation of objective tumor response in participants with CR (disappearance of all target lesions with the exception of nodal disease, all target nodes reduced to normal size (short axis <10 mm) or PR (a >=30 % decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions) according to RECIST version 1.1 to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. PD was defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

30. Progression Free Survival (PFS): Part 2 Phase 1 [baseline up to 1673 days]

    PFS was defined as the time from first dose of study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PD was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

31. Percentage of Participants With Disease Control (DC): Phase 2 [From initiation of treatment up to disease progression (up to 1526 days)]

    DC: CR, PR or stable disease (SD) for >=24 weeks according to RECIST version (v)1.1 recorded in time period between first dose of study treatment and disease progression or death to any cause. CR: disappearance of all target lesions with exception of nodal disease. All target nodes reduced to normal size (short axis <10 mm). PR: >=30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. SD was defined as not achieving an OR with confirmed CR or PR according to RECIST v1.1, as determined by investigators, relative to response evaluable population, but remained stable for at least 24 weeks after first dose, then best overall response for such a participant was considered as stable disease. PD was defined using RECIST v1.1 as a 20% increase in sum of longest diameter of target lesions, or a measurable increase in a non-target lesion, or appearance of new lesions.

32. Overall Survival (OS): Phase 2 [From initiation of treatment up to follow-up period (up to 1526 days)]

    Overall survival was defined as the time from first dose of study treatment to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. OS was estimated with Kaplan-Meier method.

33. Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment [Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, End of treatment (up to 1526 days)]

    The functional assessment of cancer therapy (FACT) is a modular approach to assess participant's health-related quality of life. FACT-B total score was derived from the sum of these 5 sub-scale scores: physical well-being, social/family well-being and functional well-being (all 3 sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life), emotional well-being (consists of 6 items and ranging from 0 to 24, where higher scores indicating better quality of life, and a breast cancer subscale (consists of 9 items and ranging from 0 to 36, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. FACT-B total score range was of 0 (not at all good) to 144 (very well), where higher scores indicating better quality of life.

34. Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment [Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, End of treatment (up to 1526 days)]

    FACT is a modular approach to assess participant's health-related quality of life. FACT-G total score was derived from the sum of these 4 sub-scale scores: physical well-being, social/family well-being and functional well-being (all 3 sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life), emotional well-being (consists of 6 items and ranging from 0 to 24, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. FACT-G total score range was of 0 (not at all good) to 108 (very well), where higher scores indicating better quality of life.

35. Change From Baseline in Trial Outcome Index (TOI): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment [Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, End of treatment (up to 1526 days)]

    FACT is a modular approach to assess participant's health-related quality of life. TOI total score was derived from the sum of the 3 sub-scale scores: physical well-being, functional well-being (both sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life) and breast cancer subscale (consists of 9 items and ranging from 0 to 36, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. TOI total score range was of 0 (not at all good) to 92 (very well), where higher scores indicating better quality of life.

36. Presence of Tumor Tissue Biomarker- Ki67: Phase 2 [Baseline (Day 1)]

    Tumor tissue biomarker, Ki67 was analyzed to investigate possible associations with resistance or sensitivity to treatment with study drugs and was selected based on its known relevance to mechanisms involved in cell cycle regulation. Number of participants with less than or equal to and greater than 20 percent of Ki67 tumor tissue biomarker were reported.

37. Presence of Tumor Tissue Biomarkers- Estrogen Receptor (ER) H-Score, Retinoblastoma (Rb) H-Score, B-cell Lymphoma-1 (BCL-1) H-Score, P16 H-Score: Phase 2 [Baseline (Day 1)]

    Tumor tissue biomarkers ER, Rb, BCL-1 and P16 were analyzed to investigate possible associations with resistance or sensitivity to treatment with study drugs and were selected based on their known relevance to mechanisms involved in cell cycle regulation. Number of participants with positive ER (H-Score), Rb (H-Score), BCL-1 (H-Score) and P16 (H-Score) tumor tissue biomarkers were reported. The H-score is a method of assessing the extent of nuclear immunoreactivity, applicable to steroid receptors.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Phase 1

• In Part 1, advanced solid tumor (except SCLC or retinoblastoma) proven histologically or cytologically at original diagnosis, that is refractory to standard therapy or for whom no standard of care therapy is available.

• In Part 2 and Phase 2, post menopausal women with proven diagnosis of ER-positive, HER2-negative adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease (including bone only disease) not amenable to resection or radiation therapy with curative intent and for whom chemotherapy is not clinically indicated.

• Adequate blood cell counts, kidney function and liver function and and Eastern Cooperative Oncology Group [ECOG] score of 0 or 1.

• Resolved acute effects of any prior therapy to baseline severity or Grade ≤1

Phase 2

• Adult women (≥ 20 years of age) with proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent and for whom chemotherapy is not clinically indicated.

• Documentation of histologically or cytologically confirmed diagnosis of ER(+) breast cancer based on local laboratory results.

• Adequate blood cell counts, kidney function and liver function and and Eastern Cooperative Oncology Group [ECOG] score of 0 to 2.

Exclusion Criteria:

Phase 1

• Active uncontrolled or symptomatic CNS metastases.

• Uncontrolled infection, unstable or sever intercurrent medical condition, or current drug or alcohol abuse

• Active or unstable cardiac disease or history of heart attack within 6 months

Phase 2

• HER2 positive tumor based on local laboratory results utilizing one of the sponsor approved assays.

• Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease.

• Prior neoadjuvant or adjuvant treatment with a non steroidal aromatase inhibitor (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aichi Cancer Center Hospital	Nagoya	Aichi	Japan	464-8681
2	National Cancer Center Hospital East	Kashiwa	Chiba	Japan	277-8577
3	National Hospital Organization Hokkaido Cancer Center	Sapporo	Hokkaido	Japan	003-0804
4	Kumamoto Shinto General Hospital	Kumamoto-city	Kumamoto	Japan	862-8655
5	Saitama Cancer Center	Kita-adachi-gun	Saitama	Japan	362-0806
6	National Cancer Center Hospital	Chuo-Ku	Tokyo	Japan	104-0045
7	Chiba Cancer Center	Chiba		Japan	260-8717
8	National Hospital Organization Shikoku Cancer Center	Ehime		Japan	791-0280
9	National Hospital Organization Kyushu Cancer Center	Fukuoka		Japan	811-1395
10	Hiroshima City Hiroshima Citizens Hospital	Hiroshima		Japan	730-8518
11	Iwate Medical University Hospital	Iwate		Japan	020-8505
12	Hakuaikai Medical Corporation Sagara Hospital	Kagoshima		Japan	892-0833
13	Kumamoto University Hospital	Kumamoto		Japan	860-8556
14	Kumamoto City Hospital	Kumamoto		Japan	862-8505
15	Kyoto University Hospital	Kyoto		Japan	606-8507
16	National Hospital Organization Osaka National Hospital	Osaka		Japan	540-0006

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01684215
• Other Study ID Numbers: A5481010
• First Posted: Sep 12, 2012
• Last Update Posted: Nov 23, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Pfizer: Phase 1/2; PD-0332991; palbociclib; Cyclin Dependent Kinase 4/6 inhibitor; Japanese; solid tumors; breast cancer; A5481010
• Additional relevant MeSH terms: Breast Neoplasms; Neoplasms; Letrozole; Palbociclib

Study Results

Participant Flow

Pre-assignment Detail	Study comprised of 2 phases: Participants were enrolled to dose escalation cohorts (PD-0332991 100 milligram [mg] and 125 mg) in Phase 1 Part 1, to maximum tolerated dose (MTD) cohort (PD-0332991 125 mg+ Letrozole 2.5 mg) in Phase 1 Part 2 and to expanded cohort (PD-0332991 125 mg and Letrozole 2.5 mg) in Phase 2.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Period Title: Phase 1, Part 1
STARTED	6	6	0	0
Treated	6	6	0	0
COMPLETED	0	0	0	0
NOT COMPLETED	6	6	0	0
Period Title: Phase 1, Part 1
STARTED	0	0	6	0
COMPLETED	0	0	0	0
NOT COMPLETED	0	0	6	0
Period Title: Phase 1, Part 1
STARTED	0	0	0	43
Treated	0	0	0	42
COMPLETED	0	0	0	0
NOT COMPLETED	0	0	0	43

Baseline Characteristics

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort	Total
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	Total of all reporting groups
Overall Participants	6	6	6	42	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	4 66.7%	5 83.3%	4 66.7%	26 61.9%	39 65%
>=65 years	2 33.3%	1 16.7%	2 33.3%	16 38.1%	21 35%
Sex: Female, Male (Count of Participants)
Female	5 83.3%	2 33.3%	6 100%	42 100%	55 91.7%
Male	1 16.7%	4 66.7%	0 0%	0 0%	5 8.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicities (DLT): Part 1 Phase 1
Description	DLT was classified as per common terminology criteria for adverse events (CTCAE) version 4.0 as any of the events occurring during 28 days of Cycle 1,attributed to study drug:grade 4 neutropenia(for a duration of greater than [>]7 days); febrile neutropenia (grade greater than or equal to [>=]3 neutropenia,body temperature >=38.5 degree Celsius);grade >=3 thrombocytopenia with bleeding episode;grade 4 thrombocytopenia;grade >=3 non-hematologic toxicity except grade 3 or more nausea, vomiting,electrolyte abnormality(if controllable by therapy);grade 3 QTc prolongation(>500 millisecond [msec])persist after correction of reversible cause such as electrolyte abnormalities or hypoxia. Lack of hematologic recovery (platelets less than [<]50,000/microliter [mcL],absolute neutrophil count <1,000/mcL,hemoglobin <8.0 gram/deciliter [g/dL]) or prolonged non hematologic toxicities that delays initiation of next dose by >7 days;receipt of <75 percent of planned dose in first cycle due to toxicity.
Time Frame	Lead-in period (Day -7) up to Day 28 (Cycle 1)

Outcome Measure Data

Analysis Population Description

DLT analysis set included all participants whom DLTs were evaluable in Part 1 Phase 1.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Count of Participants [Participants]	1 16.7%	1 16.7%

2. Primary Outcome

Title	Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 Phase 1
Description	A treatment related AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Relatedness was judged by investigator. AEs included both serious and non-serious adverse events.
Time Frame	Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort
Arm/Group Description	In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6
AEs	6 100%
SAEs	2 33.3%

3. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) By Severity: Part 2 Phase 1
Description	AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment but increased in National Cancer Institute (NCI) CTCAE grade during study treatment period. AE severity was defined to be the maximum toxicity grade of the TEAEs experienced by the participants during the study. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).
Time Frame	Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort
Arm/Group Description	In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6
Grade 1	0 0%
Grade 2	0 0%
Grade 3	4 66.7%
Grade 4	2 33.3%
Grade 5	0 0%

4. Primary Outcome

Title	Percentage of Participants With 1 Year Progression Free Survival (PFS): Phase 2
Description	PFS was defined as the time from first dose of study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurred first. PD was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.1-year PFS was defined as the percentage of participants without PFS events (PD or death due to any cause) at 12 months based on the Kaplan-Meier estimate. Percentage of participants with 1-year PFS with 90% confidence interval (CI) were reported.
Time Frame	From initiation of treatment up to 12 months

Outcome Measure Data

Analysis Population Description

Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	42
Number (90% Confidence Interval) [percentage of participants]	75.6 1260%

5. Secondary Outcome

Title	Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Phase 1 (Part 1) and Phase 2
Description	A treatment related AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Relatedness was judged by investigator. AEs included both serious and non-serious adverse events.
Time Frame	Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (up to 308 days), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1526 days)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6	42
AEs	6 100%	5 83.3%	42 700%
SAEs	0 0%	0 0%	2 33.3%

6. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) By Severity: Phase 1 (Part 1) and Phase 2
Description	AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment but increased in NCI CTCAE version 4.0 grade during study treatment period. AE severity was defined to be the maximum toxicity grade of the TEAEs experienced by the participants during the study. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).
Time Frame	Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (up to 308 days), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1526 days)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6	42
Grade 1	0 0%	1 16.7%	0 0%
Grade 2	0 0%	1 16.7%	2 33.3%
Grade 3	4 66.7%	3 50%	29 483.3%
Grade 4	2 33.3%	1 16.7%	10 166.7%
Grade 5	0 0%	0 0%	1 16.7%

7. Secondary Outcome

Title	Number of Participants With Clinically Significant Laboratory Abnormalities
Description	Abnormality criteria: hemoglobin: <0.8*lower limit of normal [LLN], platelets: <0.5*LLN or >1.75*upper limit of normal [ULN], leukocytes: <0.6*LLN or >1.5*ULN, lymphocytes, total neutrophils: <0.8*LLN or >1.2*ULN, basophils, eosinophil,monocytes: >1.2*ULN); aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase (GT): >0.3*ULN, total protein, albumin: <0.8*LLN or >1.2*ULN, total bilirubin, direct bilirubin: >1.5*ULN; blood urea nitrogen, creatinine: >1.3*ULN, uric acid: >1.2*ULN; sodium: <0.95*LLN or >1.05*ULN, potassium, chloride, calcium, magnesium: <0.9*LLN or >1.1*ULN, phosphate: <0.8*LLN or >1.2*ULN; creatine kinase: >2.0*ULN, glucose fasting: <0.6*LLN or >1.5*ULN, glycosylated haemoglobin: >1.3*ULN;urinalysis dipstick (urine protein, urine blood >=1); urine protein 24 hour: >1.1*ULN; coagulation Activated partial thromboplastin time [APTT], Prothrombin, prothrombin international ratio: >1.1*ULN.
Time Frame	Part 1 Phase 1: Lead-in period (Day -7) up to 308 days; Part 2 Phase 1: Baseline (Day 1) up to 1673 days; Phase 2: Baseline (Day 1) up to 1526 days

Outcome Measure Data

Analysis Population Description

Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6	6	42
Count of Participants [Participants]	6 100%	6 100%	6 100%	40 95.2%

8. Secondary Outcome

Title	Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991 Following Multiple Dose: Part 1 Phase 1
Description	AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.
Time Frame	Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*hr/mL)]	1276 (45)	2838 (43)

9. Secondary Outcome

Title	AUCtau Dose Normalized to 125 Milligram (mg) of PD-0332991 Following Multiple Dose: Part 1 Phase 1
Description	AUCtau Dose Normalized to 125 mg is area under the plasma concentration-time curve over dosing interval dose normalized to 125 mg which is calculated by log-linear trapezoidal method.
Time Frame	Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	1595 (45)	2838 (43)

10. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From 0 to Time 24 Hours (AUC24) of PD-0332991 Following Single Dose: Part 1 Phase 1
Description	AUC24 is area under the plasma concentration-time curve from 0 to time 24 hours which is calculated by log-linear trapezoidal method.
Time Frame	Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12 and 24 hours post-dose in Lead-in period (Day -7)

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	547.5 (19)	1322 (42)

11. Secondary Outcome

Title	AUC24 Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1
Description	AUC24 Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to time 24 hours dose normalized to 125 mg which is calculated by log-linear trapezoidal method.
Time Frame	Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12 and 24 hours post-dose in Lead-in period (Day -7)

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	684.5 (19)	1322 (42)

12. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of PD-0332991 Following Single Dose: Part 1 Phase 1
Description	AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.
Time Frame	Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	1039 (32)	2483 (49)

13. Secondary Outcome

Title	AUCinf Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1
Description	AUCinf Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to infinity dose normalized to 125 mg which is calculated by log-linear trapezoidal method.
Time Frame	Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	1296 (32)	2483 (49)

14. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From 0 to Time of Last Measurable Concentration (AUClast) of PD-0332991 Following Single Dose: Part 1 Phase 1
Description	AUClast is area under the plasma concentration-time curve from 0 to time of last measurable concentration which is calculated by log-linear trapezoidal method.
Time Frame	Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	971.7 (31)	2396 (48)

15. Secondary Outcome

Title	AUClast Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1
Description	AUClast Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to time of last measurable concentration dose normalized to 125 mg which is calculated by log-linear trapezoidal method.
Time Frame	Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	1215 (31)	2396 (48)

16. Secondary Outcome

Title	Apparent Oral Clearance of PD-0332991: Part 1 Phase 1
Description	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by AUCinf. AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.
Time Frame	Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Single dose	96.43 (32)	50.29 (49)
Multiple dose	78.43 (45)	44.03 (43)

17. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) Of PD-0332991: Part 1 Phase 1
Description	Cmax is maximum plasma concentration which is observed directly from the actual time-concentration data.
Time Frame	Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Single dose	41.37 (15)	104.1 (39)
Multiple dose	77.36 (33)	185.5 (27)

18. Secondary Outcome

Title	Cmax Dose Normalized to 125 mg of PD-0332991: Part 1 Phase 1
Description	Cmax Dose Normalized to 125 mg is maximum plasma concentration dose normalized to 125 mg which is observed directly from the actual time-concentration data.
Time Frame	Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Single dose	51.74 (15)	104.1 (39)
Multiple dose	96.72 (33)	185.5 (27)

19. Secondary Outcome

Title	Pre-dose Plasma Concentration (Ctrough) of PD-0332991 Following Multiple Dose: Part 1 Phase 1
Description	Ctrough is pre-dose concentration during multiple dosing which is observed directly from the actual time-concentration data.
Time Frame	Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	35.51 (59)	72.76 (48)

20. Secondary Outcome

Title	Accumulation Ratio (Rac) of PD-0332991 Following Multiple Dose: Part 1 Phase 1
Description	Rac is the ratio of AUCtau (after multiple doses) to AUCtau (after single dose). AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.
Time Frame	Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Median (Full Range) [ratio]	2.060	1.855

21. Secondary Outcome

Title	Linearity (Rss) of PD-0332991 Following Multiple Dose: Part 1 Phase 1
Description	Rss is the ratio of AUCtau (after multiple doses) to AUCinf (after single dose). AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method. AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.
Time Frame	Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Median (Full Range) [ratio]	1.130	1.105

22. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991: Part 1 Phase 1
Description	Tmax is time at which maximum plasma concentration (Cmax) was observed. It was observed directly from data as time of first occurrence.
Time Frame	Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Single dose	5.02	4.00
Multiple dose	4.02	4.02

23. Secondary Outcome

Title	Terminal Half-Life (t1/2) of PD-0332991: Part 1 Phase 1
Description	t1/2 is terminal elimination half-life which is calculated by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time Frame	Single dose: 0 hour (pre-dose),1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7), Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Single dose	25.72 (5.2632)	23.93 (2.6882)
Multiple dose	23.75 (6.7778)	23.15 (7.7045)

24. Secondary Outcome

Title	Volume of Distribution (Vz/F) of PD-0332991 Following Single Dose: Part 1 Phase 1
Description	Vz/F is apparent volume of distribution estimated from terminal phase, which is calculated as CL/F/kel. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method (AUCinf). kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Time Frame	Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [liter]	3514 (25)	1730 (41)

25. Secondary Outcome

Title	Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991: Phase 2
Description	AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.
Time Frame	0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	1979 (16)

26. Secondary Outcome

Title	Apparent Oral Clearance of PD-0332991: Phase 2
Description	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. It was calculated by dividing the given oral dose by AUCtau. AUCtau is the area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.
Time Frame	0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [L/hr]	63.21 (16)

27. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) Of PD-0332991: Phase 2
Description	Cmax is maximum plasma concentration which is observed directly from the actual time-concentration data.
Time Frame	0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	124.7 (26)

28. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991: Phase 2
Description	Tmax is time at which maximum plasma concentration (Cmax) was observed. It was observed directly from data as time of first occurrence.
Time Frame	0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6
Median (Full Range) [hour]	4.90

29. Secondary Outcome

Title	Pre-dose Plasma Concentration (Ctrough) of PD-0332991: Phase 2
Description	Ctrough is pre-dose concentration during multiple dosing which is observed directly from the actual time-concentration data.
Time Frame	0 (pre-dose), 1, 2, 4, 6, 8, 10, 24 hours post dose on Cycle 1 Day 15

Outcome Measure Data

Analysis Population Description

PK parameter analysis set included treated participants who had at least 1 of the PK parameters of primary interest in at least 1 PK sampling period.

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	59.75 (38)

30. Secondary Outcome

Title	Percentage of Participants With Objective Response: Phase 1
Description	Objective response (OR) was defined as a complete response (CR) or partial response (PR) according to the RECIST version 1.1 recorded from first dose of study treatment until disease progression or death due to any cause. CR was defined as disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis <10 millimeter [mm]). PR was defined as a >=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Percentage of participants with objective response (who achieved CR or PR) were reported.
Time Frame	From initiation of treatment up to disease progression (up to 30 months)

Outcome Measure Data

Analysis Population Description

Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6	6	6
With Complete Response	0 0%	0 0%	0 0%
With Partial Response	0 0%	0 0%	33.3 555%

31. Secondary Outcome

Title	Percentage of Participants With Objective Response: Phase 2
Description	Objective response was defined as a complete response (CR) or partial response (PR) according to the RECIST version 1.1 recorded from first dose of study treatment until disease progression or death due to any cause. PD was defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. CR was defined as disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis <10 mm). PR was defined as a >=30% decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Percentage of participants with objective response (who achieved CR or PR) were reported.
Time Frame	From initiation of treatment up to disease progression (up to 1526 days)

Outcome Measure Data

Analysis Population Description

Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	42
Number [percentage of participants]	47.6 793.3%

32. Secondary Outcome

Title	Duration of Response (DOR): Part 2 Phase 1
Description	Duration of response was defined as the interval from the first documentation of objective tumor response in participants with CR (disappearance of all target lesions with the exception of nodal disease. All target nodes reduced to normal size (short axis <10 millimeter [mm]) or PR (a >=30 percent decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions) according to RECIST version 1.1 to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first.
Time Frame	baseline up to 1673 days

Outcome Measure Data

Analysis Population Description

Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991). Data for this outcome measure was not summarized and individual participant's data was reported. Here, number of participants analyzed (N) signifies the participants evaluable for this outcome measure.

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort
Arm/Group Description	In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	2
Participant 1	1509
Participant 2	1428

33. Secondary Outcome

Title	Duration of Response (DOR): Phase 2
Description	Duration of response was defined as the interval from the first documentation of objective tumor response in participants with CR (disappearance of all target lesions with the exception of nodal disease, all target nodes reduced to normal size (short axis <10 mm) or PR (a >=30 % decrease in sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions) according to RECIST version 1.1 to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. PD was defined using RECIST v1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	From initiation of treatment up to disease progression (up to 1526 days)

Outcome Measure Data

Analysis Population Description

Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991). Here, "Overall Number of Participants Analyzed" (N) signifies the participants evaluable for this outcome measure.

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	20
Median (95% Confidence Interval) [months]	41.4

34. Secondary Outcome

Title	Progression Free Survival (PFS): Part 2 Phase 1
Description	PFS was defined as the time from first dose of study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PD was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	baseline up to 1673 days

Outcome Measure Data

Analysis Population Description

Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991). Data for this outcome measure was not summarized and individual participant's data was reported.

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort
Arm/Group Description	In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	6
Participant 1	1590
Participant 2	1593
Participant 3	1602
Participant 4	36
Participant 5	31
Participant 6	1512

35. Secondary Outcome

Title	Percentage of Participants With Disease Control (DC): Phase 2
Description	DC: CR, PR or stable disease (SD) for >=24 weeks according to RECIST version (v)1.1 recorded in time period between first dose of study treatment and disease progression or death to any cause. CR: disappearance of all target lesions with exception of nodal disease. All target nodes reduced to normal size (short axis <10 mm). PR: >=30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. SD was defined as not achieving an OR with confirmed CR or PR according to RECIST v1.1, as determined by investigators, relative to response evaluable population, but remained stable for at least 24 weeks after first dose, then best overall response for such a participant was considered as stable disease. PD was defined using RECIST v1.1 as a 20% increase in sum of longest diameter of target lesions, or a measurable increase in a non-target lesion, or appearance of new lesions.
Time Frame	From initiation of treatment up to disease progression (up to 1526 days)

Outcome Measure Data

Analysis Population Description

Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	42
Number [percentage of participants]	85.7 1428.3%

36. Secondary Outcome

Title	Overall Survival (OS): Phase 2
Description	Overall survival was defined as the time from first dose of study treatment to date of death due to any cause. In the absence of confirmation of death, survival time was censored to last date the participant was known to be alive. OS was estimated with Kaplan-Meier method.
Time Frame	From initiation of treatment up to follow-up period (up to 1526 days)

Outcome Measure Data

Analysis Population Description

Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	42
Median (95% Confidence Interval) [months]	NA

37. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment
Description	The functional assessment of cancer therapy (FACT) is a modular approach to assess participant's health-related quality of life. FACT-B total score was derived from the sum of these 5 sub-scale scores: physical well-being, social/family well-being and functional well-being (all 3 sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life), emotional well-being (consists of 6 items and ranging from 0 to 24, where higher scores indicating better quality of life, and a breast cancer subscale (consists of 9 items and ranging from 0 to 36, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. FACT-B total score range was of 0 (not at all good) to 144 (very well), where higher scores indicating better quality of life.
Time Frame	Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, End of treatment (up to 1526 days)

Outcome Measure Data

Analysis Population Description

Patient reported outcome (PRO) analysis set included all enrolled participants who receive at least 1 dose of study drug with both baseline and at least 1 complete post-baseline PRO assessment. "Number analyzed" signifies number of participants evaluable for specified time points.

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	42
Baseline	106.46
Change at Cycle 2: Day 1	-1.20
Change at Cycle 3: Day 1	-2.22
Change at Cycle 5: Day 1	-2.38
Change at Cycle 7: Day 1	-4.62
Change at Cycle 9: Day 1	-4.45
Change at Cycle 11: Day 1	-4.48
Change at Cycle 13: Day 1	-6.32
Change at Cycle 15: Day 1	-4.06
Change at Cycle 17: Day 1	-6.07
Change at Cycle 19: Day 1	-7.39
Change at Cycle 21: Day 1	-5.85
Change at Cycle 23: Day 1	-5.89
Change at Cycle 25: Day 1	-4.22
Change at Cycle 27: Day 1	-4.76
Change at Cycle 29: Day 1	-6.26
Change at Cycle 31: Day 1	-5.13
Change at Cycle 33: Day 1	-7.12
Change at Cycle 35: Day 1	-7.68
Change at Cycle 37: Day 1	-8.07
Change at Cycle 39: Day 1	-6.87
Change at Cycle 41: Day 1	-5.70
Change at Cycle 43: Day 1	-10.42
Change at Cycle 45: Day 1	-7.94
Change at Cycle 47: Day 1	-8.56
Change at Cycle 49: Day 1	-10.58
End of Treatment	-9.17

38. Secondary Outcome

Title	Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment
Description	FACT is a modular approach to assess participant's health-related quality of life. FACT-G total score was derived from the sum of these 4 sub-scale scores: physical well-being, social/family well-being and functional well-being (all 3 sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life), emotional well-being (consists of 6 items and ranging from 0 to 24, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. FACT-G total score range was of 0 (not at all good) to 108 (very well), where higher scores indicating better quality of life.
Time Frame	Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, End of treatment (up to 1526 days)

Outcome Measure Data

Analysis Population Description

Patient reported outcome (PRO) analysis set included all enrolled participants who receive at least 1 dose of study drug with both baseline and at least 1 complete post-baseline PRO assessment. "Number analyzed" signifies number of participants evaluable for specified time points.

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	42
Baseline	80.22
Change at Cycle 2: Day 1	-1.15
Change at Cycle 3: Day 1	-1.34
Change at Cycle 5: Day 1	-0.36
Change at Cycle 7: Day 1	-3.56
Change at Cycle 9: Day 1	-2.39
Change at Cycle 11: Day 1	-3.94
Change at Cycle 13: Day 1	-4.74
Change at Cycle 15: Day 1	-2.98
Change at Cycle 17: Day 1	-4.64
Change at Cycle 19: Day 1	-5.48
Change at Cycle 21: Day 1	-4.34
Change at Cycle 23: Day 1	-4.39
Change at Cycle 25: Day 1	-3.22
Change at Cycle 27: Day 1	-3.80
Change at Cycle 29: Day 1	-4.52
Change at Cycle 31: Day 1	-4.55
Change at Cycle 33: Day 1	-6.67
Change at Cycle 35: Day 1	-6.63
Change at Cycle 37: Day 1	-6.49
Change at Cycle 39: Day 1	-5.07
Change at Cycle 41: Day 1	-5.06
Change at Cycle 43: Day 1	-7.08
Change at Cycle 45: Day 1	-5.94
Change at Cycle 47: Day 1	-6.22
Change at Cycle 49: Day 1	-8.58
End of Treatment	-7.09

39. Secondary Outcome

Title	Change From Baseline in Trial Outcome Index (TOI): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment
Description	FACT is a modular approach to assess participant's health-related quality of life. TOI total score was derived from the sum of the 3 sub-scale scores: physical well-being, functional well-being (both sub-scales consisting of 7 items ranging from 0 to 28, where higher scores indicating better quality of life) and breast cancer subscale (consists of 9 items and ranging from 0 to 36, where higher scores indicating better quality of life). Each individual item was rated on a 5-point Likert scale, ranging from 0 (not at all good) to 4 (very well), where higher scores indicating better quality of life. TOI total score range was of 0 (not at all good) to 92 (very well), where higher scores indicating better quality of life.
Time Frame	Baseline (Day 1 of Cycle 1), Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, End of treatment (up to 1526 days)

Outcome Measure Data

Analysis Population Description

Patient reported outcome (PRO) analysis set included all enrolled participants who receive at least 1 dose of study drug with both baseline and at least 1 complete post-baseline PRO assessment. "Number analyzed" signifies number of participants evaluable for specified time points.

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	42
Baseline	71.52
Change at Cycle 2: Day 1	-1.17
Change at Cycle 3: Day 1	-2.20
Change at Cycle 5: Day 1	-2.54
Change at Cycle 7: Day 1	-3.63
Change at Cycle 9: Day 1	-3.31
Change at Cycle 11: Day 1	-2.30
Change at Cycle 13: Day 1	-3.93
Change at Cycle 15: Day 1	-2.49
Change at Cycle 17: Day 1	-3.18
Change at Cycle 19: Day 1	-4.32
Change at Cycle 21: Day 1	-3.56
Change at Cycle 23: Day 1	-3.19
Change at Cycle 25: Day 1	-2.13
Change at Cycle 27: Day 1	-2.50
Change at Cycle 29: Day 1	-3.70
Change at Cycle 31: Day 1	-1.95
Change at Cycle 33: Day 1	-4.30
Change at Cycle 35: Day 1	-4.65
Change at Cycle 37: Day 1	-4.84
Change at Cycle 39: Day 1	-3.47
Change at Cycle 41: Day 1	-2.27
Change at Cycle 43: Day 1	-7.00
Change at Cycle 45: Day 1	-3.00
Change at Cycle 47: Day 1	-4.00
Change at Cycle 49: Day 1	-2.00
End of Treatment	-6.03

40. Secondary Outcome

Title	Presence of Tumor Tissue Biomarker- Ki67: Phase 2
Description	Tumor tissue biomarker, Ki67 was analyzed to investigate possible associations with resistance or sensitivity to treatment with study drugs and was selected based on its known relevance to mechanisms involved in cell cycle regulation. Number of participants with less than or equal to and greater than 20 percent of Ki67 tumor tissue biomarker were reported.
Time Frame	Baseline (Day 1)

Outcome Measure Data

Analysis Population Description

Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	42
<=20 percent	19 316.7%
>20 percent	23 383.3%

41. Secondary Outcome

Title	Presence of Tumor Tissue Biomarkers- Estrogen Receptor (ER) H-Score, Retinoblastoma (Rb) H-Score, B-cell Lymphoma-1 (BCL-1) H-Score, P16 H-Score: Phase 2
Description	Tumor tissue biomarkers ER, Rb, BCL-1 and P16 were analyzed to investigate possible associations with resistance or sensitivity to treatment with study drugs and were selected based on their known relevance to mechanisms involved in cell cycle regulation. Number of participants with positive ER (H-Score), Rb (H-Score), BCL-1 (H-Score) and P16 (H-Score) tumor tissue biomarkers were reported. The H-score is a method of assessing the extent of nuclear immunoreactivity, applicable to steroid receptors.
Time Frame	Baseline (Day 1)

Outcome Measure Data

Analysis Population Description

Full analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Measure Participants	42
ER (H-Score)	41 683.3%
Rb (H-Score)	41 683.3%
BCL-1 (H-Score)	42 700%
P16 (H-Score)	41 683.3%

Adverse Events

Time Frame	Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (up to 308 days), Part 2 Phase 1: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1526 days)
Adverse Event Reporting Description	Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non serious in another participant, or 1 participant may have experienced both a serious and non serious event during the study. Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).
Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort		PD-0332991 125 mg: Dose Escalation Cohort		PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort		PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.		In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.		In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.		In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
All Cause Mortality
	PD-0332991 100 mg: Dose Escalation Cohort		PD-0332991 125 mg: Dose Escalation Cohort		PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort		PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	PD-0332991 100 mg: Dose Escalation Cohort		PD-0332991 125 mg: Dose Escalation Cohort		PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort		PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		2/6 (33.3%)		4/42 (9.5%)
Blood and lymphatic system disorders
Febrile Neutropenia	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/42 (2.4%)
Cardiac disorders
Supraventricular tachycardia	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Gastrointestinal disorders
Gastrointestinal perforation	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Vomiting	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/42 (2.4%)
General disorders
Malaise	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/42 (2.4%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/42 (2.4%)
Nervous system disorders
Cerebral Haemorrhage	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/42 (2.4%)
Dizziness	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/42 (2.4%)
Subarachnoid Haemorrhage	0/6 (0%)		0/6 (0%)		0/6 (0%)		1/42 (2.4%)
Other (Not Including Serious) Adverse Events
	PD-0332991 100 mg: Dose Escalation Cohort		PD-0332991 125 mg: Dose Escalation Cohort		PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort		PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		6/6 (100%)		6/6 (100%)		42/42 (100%)
Blood and lymphatic system disorders
Anaemia	0/6 (0%)		2/6 (33.3%)		0/6 (0%)		10/42 (23.8%)
Leukopenia	0/6 (0%)		0/6 (0%)		0/6 (0%)		5/42 (11.9%)
Neutropenia	0/6 (0%)		0/6 (0%)		0/6 (0%)		9/42 (21.4%)
Cardiac disorders
Palpitations	0/6 (0%)		0/6 (0%)		0/6 (0%)		4/42 (9.5%)
Mitral valve incompetence	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Supraventricular tachycardia	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Eye disorders
Conjunctival haemorrhage	0/6 (0%)		0/6 (0%)		2/6 (33.3%)		2/42 (4.8%)
Lacrimation increased	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/42 (2.4%)
Macular oedema	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Vision blurred	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Gastrointestinal disorders
Constipation	1/6 (16.7%)		2/6 (33.3%)		2/6 (33.3%)		12/42 (28.6%)
Nausea	1/6 (16.7%)		1/6 (16.7%)		2/6 (33.3%)		9/42 (21.4%)
Stomatitis	0/6 (0%)		2/6 (33.3%)		1/6 (16.7%)		32/42 (76.2%)
Vomiting	1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		5/42 (11.9%)
Cheilitis	0/6 (0%)		0/6 (0%)		0/6 (0%)		5/42 (11.9%)
Dental caries	0/6 (0%)		0/6 (0%)		0/6 (0%)		4/42 (9.5%)
Diarrhoea	1/6 (16.7%)		4/6 (66.7%)		4/6 (66.7%)		5/42 (11.9%)
Abdominal discomfort	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Abdominal distension	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Abdominal pain upper	1/6 (16.7%)		0/6 (0%)		2/6 (33.3%)		1/42 (2.4%)
Food poisoning	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Glossitis	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/42 (2.4%)
Abdominal pain	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/42 (0%)
Anal haemorrhage	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/42 (0%)
Dyspepsia	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/42 (0%)
Gastritis	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		3/42 (7.1%)
General disorders
Malaise	2/6 (33.3%)		0/6 (0%)		0/6 (0%)		9/42 (21.4%)
Influenza like illness	0/6 (0%)		0/6 (0%)		0/6 (0%)		5/42 (11.9%)
Pain	0/6 (0%)		0/6 (0%)		0/6 (0%)		3/42 (7.1%)
Pyrexia	0/6 (0%)		1/6 (16.7%)		2/6 (33.3%)		3/42 (7.1%)
Chest discomfort	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Fatigue	0/6 (0%)		2/6 (33.3%)		2/6 (33.3%)		2/42 (4.8%)
Mucosal inflammation	0/6 (0%)		0/6 (0%)		2/6 (33.3%)		1/42 (2.4%)
Oedema peripheral	1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
General physical health deterioration	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/42 (0%)
Non-cardiac chest pain	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/42 (0%)
Immune system disorders
Seasonal allergy	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Infections and infestations
Nasopharyngitis	1/6 (16.7%)		0/6 (0%)		2/6 (33.3%)		19/42 (45.2%)
Upper respiratory tract infection	0/6 (0%)		0/6 (0%)		2/6 (33.3%)		6/42 (14.3%)
Angular cheilitis	0/6 (0%)		0/6 (0%)		0/6 (0%)		4/42 (9.5%)
Cellulitis	0/6 (0%)		0/6 (0%)		0/6 (0%)		4/42 (9.5%)
Conjunctivitis	0/6 (0%)		0/6 (0%)		0/6 (0%)		4/42 (9.5%)
Oral herpes	0/6 (0%)		0/6 (0%)		0/6 (0%)		3/42 (7.1%)
Pharyngitis	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		8/42 (19%)
Influenza	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/42 (2.4%)
Skin infection	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Urinary tract infection	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/42 (2.4%)
Cystitis	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		2/42 (4.8%)
Lung infection	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/42 (0%)
Injury, poisoning and procedural complications
Fall	0/6 (0%)		0/6 (0%)		4/6 (66.7%)		9/42 (21.4%)
Contusion	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		3/42 (7.1%)
Femur fracture	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/42 (0%)
Investigations
Alanine aminotransferase increased	1/6 (16.7%)		1/6 (16.7%)		2/6 (33.3%)		12/42 (28.6%)
Aspartate aminotransferase increased	2/6 (33.3%)		1/6 (16.7%)		2/6 (33.3%)		11/42 (26.2%)
Neutrophil count decreased	5/6 (83.3%)		4/6 (66.7%)		6/6 (100%)		34/42 (81%)
Platelet count decreased	1/6 (16.7%)		2/6 (33.3%)		4/6 (66.7%)		9/42 (21.4%)
Weight decreased	1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)		5/42 (11.9%)
White blood cell count decreased	4/6 (66.7%)		5/6 (83.3%)		6/6 (100%)		30/42 (71.4%)
Blood creatinine increased	2/6 (33.3%)		0/6 (0%)		1/6 (16.7%)		2/42 (4.8%)
Activated partial thromboplastin time prolonged	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/42 (0%)
Blood alkaline phosphatase increased	2/6 (33.3%)		2/6 (33.3%)		0/6 (0%)		0/42 (0%)
Blood bilirubin increased	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/42 (0%)
Electrocardiogram QT prolonged	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/42 (0%)
Gamma-glutamyltransferase increased	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/42 (0%)
Lymphocyte count decreased	1/6 (16.7%)		3/6 (50%)		0/6 (0%)		2/42 (4.8%)
Metabolism and nutrition disorders
Decreased appetite	1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		6/42 (14.3%)
Hypocalcaemia	1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Hypoglycaemia	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Hypercalcaemia	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/42 (0%)
Hypermagnesaemia	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/42 (0%)
Hypoalbuminaemia	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/42 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		4/42 (9.5%)
Myalgia	0/6 (0%)		0/6 (0%)		0/6 (0%)		4/42 (9.5%)
Arthralgia	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		5/42 (11.9%)
Osteoporosis	0/6 (0%)		0/6 (0%)		0/6 (0%)		3/42 (7.1%)
Pain in extremity	0/6 (0%)		0/6 (0%)		0/6 (0%)		4/42 (9.5%)
Back pain	1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)		2/42 (4.8%)
Muscle spasms	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/42 (2.4%)
Neck pain	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/42 (2.4%)
Musculoskeletal chest pain	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		1/42 (2.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/42 (2.4%)
Tumour pain	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/42 (0%)
Nervous system disorders
Dysgeusia	1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		4/42 (9.5%)
Headache	0/6 (0%)		1/6 (16.7%)		2/6 (33.3%)		7/42 (16.7%)
Dizziness	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		3/42 (7.1%)
Parosmia	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Peripheral sensory neuropathy	1/6 (16.7%)		0/6 (0%)		2/6 (33.3%)		0/42 (0%)
Sensory disturbance	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/42 (2.4%)
Dysaesthesia	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/42 (0%)
Psychiatric disorders
Anxiety disorder	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Insomnia	1/6 (16.7%)		1/6 (16.7%)		1/6 (16.7%)		0/42 (0%)
Anxiety	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/42 (0%)
Renal and urinary disorders
Calculus urinary	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Proteinuria	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/42 (0%)
Reproductive system and breast disorders
Genital haemorrhage	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/42 (0%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/6 (0%)		1/6 (16.7%)		0/6 (0%)		6/42 (14.3%)
Oropharyngeal pain	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		4/42 (9.5%)
Asthma	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Cough	1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		2/42 (4.8%)
Dysphonia	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Rhinitis allergic	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/42 (2.4%)
Upper respiratory tract inflammation	0/6 (0%)		0/6 (0%)		2/6 (33.3%)		1/42 (2.4%)
Upper-airway cough syndrome	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/42 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		8/42 (19%)
Dry skin	2/6 (33.3%)		0/6 (0%)		0/6 (0%)		4/42 (9.5%)
Rash	1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		8/42 (19%)
Eczema	0/6 (0%)		0/6 (0%)		0/6 (0%)		3/42 (7.1%)
Dermatitis acneiform	0/6 (0%)		0/6 (0%)		0/6 (0%)		3/42 (7.1%)
Nail disorder	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		3/42 (7.1%)
Pruritus	0/6 (0%)		0/6 (0%)		0/6 (0%)		4/42 (9.5%)
Rash maculo-papular	1/6 (16.7%)		0/6 (0%)		0/6 (0%)		3/42 (7.1%)
Dermal cyst	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/42 (2.4%)
Haemorrhage subcutaneous	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/42 (2.4%)
Palmar-plantar erythrodysaesthesia syndrome	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		2/42 (4.8%)
Vascular disorders
Hypertension	0/6 (0%)		0/6 (0%)		1/6 (16.7%)		5/42 (11.9%)
Hot Flush	0/6 (0%)		0/6 (0%)		0/6 (0%)		3/42 (7.1%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.