A Study of Palbociclib in Combination With Fulvestrant or Tamoxifen as Treatment for Metastatic Breast Cancer

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT02384239
• Collaborator: Translational Breast Cancer Research Consortium (Other), Dana-Farber Cancer Institute (Other)
• Enrollment: 70
• Locations: 9
• Arms: 2
• Actual Duration (Months): 63.4
• Patients Per Site: 7.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial studies the side effects of palbociclib when given together with fulvestrant or tamoxifen citrate in treating patients with hormone receptor positive breast cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or has spread to other places in the body (metastatic). Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hormone therapy using fulvestrant or tamoxifen citrate may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving palbociclib together with fulvestrant or tamoxifen citrate may work better in treating hormone receptor positive breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer; Hormone Receptor Positive	Drug: Palbociclib; Drug: Tamoxifen; Drug: Fulvestrant	Phase 2

Detailed Description

Patients will be randomly allocated in a 1:1 ratio to take either 100 mg or 125 mg of palbociclib. Randomized treatment assignments will be made by permuted blocks, generated by our collaborating statistician at Dana-Farber Cancer Institute.

PRIMARY OBJECTIVES:

1. To evaluate the incidence of grade 3/4 neutropenia in patients with hormone receptor positive (HR+) advanced breast cancer previously exposed to chemotherapy, treated with fulvestrant or tamoxifen (tamoxifen citrate) in combination with palbociclib at a dose of 100mg or 125mg.

SECONDARY OBJECTIVES:

1. To evaluate progression-free survival with 100 mg and 125 mg dosing of palbociclib.

2. To evaluate inhibition of retinoblastoma (RB) phosphorylation in tumor and in skin at 100 mg and 125 mg dosing of palbociclib.

3. To evaluate the correlation between inhibition of RB phosphorylation in skin and tumor.

4. To evaluate the correlation between inhibition of RB phosphorylation and progression-free survival (PFS).

5. To evaluate the objective response and clinical benefit rate of palbociclib given at 100 mg or 125 mg.

6. To evaluate the toxicity associated with palbociclib given at 100 mg and 125 mg in combination with fulvestrant or tamoxifen.

7. To evaluate markers of resistance to palbociclib and fulvestrant or tamoxifen in circulating plasma tumor deoxyribonucleic acid (DNA) (ptDNA).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive low-dose palbociclib orally (PO) on days 1-21. Patients also receive tamoxifen citrate PO on days 1-28 or fulvestrant intramuscularly (IM) on days 1 and 15 of cycle 1 and then on day 1 only in subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive high-dose palbociclib PO on days 1-21. Patients also receive tamoxifen citrate PO on days 1-28 or fulvestrant IM on days 1 and 15 of cycle 1 and then on day 1 only in subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Palbociclib in Combination With Fulvestrant or Tamoxifen as Treatment for Hormone Receptor Positive Metastatic Breast Cancer Previously Exposed to Inhibitors of the PI3K Pathway: A Phase II Study With Pharmacodynamics Markers
• Actual Study Start Date: Oct 19, 2015
• Actual Primary Completion Date: Jan 31, 2021
• Actual Study Completion Date: Jan 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Palbociclib 100mg and, fulvestrant or tamoxifen Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)	Drug: Palbociclib; Given orally (PO); Other Names: Ibrance ; Drug: Tamoxifen; Given orally (PO); Other Names: Tamoxifen 20mg ; Drug: Fulvestrant; Given by intramuscular (IM) injection.; Other Names: Faslodex
Experimental: Palbociclib 125mg and, fulvestrant or tamoxifen Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)	Drug: Palbociclib; Given orally (PO); Other Names: Ibrance ; Drug: Tamoxifen; Given orally (PO); Other Names: Tamoxifen 20mg ; Drug: Fulvestrant; Given by intramuscular (IM) injection.; Other Names: Faslodex

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Grade 3 or 4 Neutropenia [Up to 24 months]

   Grade 3/4 neutropenia as defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.03 in patients with prior exposure to 1-3 lines of chemotherapy for metastatic breast cancer

Secondary Outcome Measures

1. Progression-free Survival (PFS) [Up to 24 months]

   PFS defined as the interval from study entry to the first documented evidence of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as at least a 20% increase in the sum of the longest diameter (SLD) of target lesions, taking as reference the smallest sum SLD recorded since the treatment started and minimum 5 mm increase over the nadir, or the appearance of one or more new lesions. Patients who remain progression-free at the time of analysis will be censored at their last date of follow-up.

2. Proportion of Participants With Demonstrated Clinical Benefit [24 weeks]

   Defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) or stable disease (SD) at 24 weeks. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.

3. Proportion of Participants With an Objective Response [24 weeks]

   Defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) at 24 weeks. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.

4. Median Change in Percent Positive Cells From Baseline of Ki-67 [Up to 24 months]

   Median change in percent positive cells of Ki-67 from baseline will be reported with IQR

5. Median Change in Percent Positive Cells From Baseline of Total-Rb [Up to 24 months]

   Median change in percent positive cells of Total-Rb from baseline will be reported with interquartile range (IQR)

6. Median Change in Percent Positive Cells From Baseline of pS780-Rb [Up to 24 months]

   Median change in percent positive cells of pS780-Rb from baseline will be reported with IQR

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically proven diagnosis of breast cancer with evidence of metastatic or locally advanced disease, not amenable to resection or radiation therapy with curative intent.

• Patients 18 years of age or older, Female patients should be either:

• Postmenopausal, as defined by at least one of the following criteria:

• Age >=60 years;

• Age <60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause;

• Documented bilateral oophorectomy;

• Medically confirmed ovarian failure.

OR

• Pre/peri-menopausal, ie, not meeting the criteria for being postmenopausal who are also receiving ongoing treatment with Luteinizing hormone-releasing hormone (LHRH) agonists (goserelin or leuprolide). The first injection should occur at least two weeks before study start.

• Documentation of ER-positive and/or PR-positive tumor (≥1% positive stained cells) based on most recent tumor biopsy (unless bone-only disease,discuss with study PI if results are discordant) utilizing an assay consistent with local standards.

• Documented human epidermal growth factor receptor 2 negative (HER2-) tumor based on local testing on most recent tumor biopsy: HER2-negative tumor is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (FISH/CISH/SISH) defined as a HER2/CEP17 ratio <2 or for single probe assessment a HER2 copy number <4.

• Must have received prior treatment with an Mechanistic target of rapamycin (mTOR) or phosphatidylinositol 3-kinase (PI3K) inhibitor

• Up to 2 prior lines of chemotherapy are allowed in the metastatic setting.

• Any number of lines of prior hormone therapy are allowed

• Patients with clear progression on either tamoxifen or fulvestrant should receive the alternate agent. Patients with clear progression on both drugs are not eligible.

• Ability to have a skin and tumor biopsy. Patients without accessible tumor for biopsy will be considered on a case by case basis.

• Patients who cannot be biopsied will not be replaced (although up to 5 ineligible/inevaluable patients can be replaced)

• A patient without biopsy amenable tumor must be cleared by the PI of the study; up to 10 patients without biopsy amenable tumor will be allowed in each arm of the study.

• Patients without accessible tumor for biopsy must provide archived tumor from the most recent biopsy available

• Bone marrow, hepatic, and renal function as follows:

Adequate bone marrow function:

• leukocytes > 2500/mL

• absolute neutrophil count > 1,000/mL

• platelets > 100,000/mL"

Adequate hepatic function:

• total bilirubin within normal institutional limits (unless Gilbert's disease with elevated indirect bilirubin only)

• aspartate aminotransferase (AST) / (serum glutamic-oxaloacetic transaminase (SGOT) < 2.5 X institutional upper limit of normal

• alanine aminotransferase (ALT) / (serum glutamic-pyruvic transaminase (SGPT) < 2.5 X institutional upper limit of normal

• Adequate renal function:

• creatinine within normal institutional limits

• Measurable or evaluable disease as defined by RECIST version 1.1. Tumor lesions previously irradiated or subjected to other loco-regional therapy will only be deemed measurable if progression at the treated site after completion of therapy is clearly documented.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

• Resolution of acute toxic effects of prior therapy or surgical procedures to National Cancer Institute (NCI) CTCAE Grade <=1 (except alopecia)

• Ability to understand a written informed consent document, and the willingness to sign it

Exclusion Criteria:

• Prior treatment with any cyclin-dependent kinase (CDK) inhibitor, and/or both fulvestrant and tamoxifen in the metastatic setting with clear progression.

• Patients with advanced/metastatic, symptomatic, visceral spread, at risk of life-threatening complications in the short term by investigator assessment.

• Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated (eg, radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization .

• Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be potent CYP3A4 inducers (for examples, see the prohibited medications section), and drugs that are known to prolong the QT interval. See prohibited meds in appendix 5.

• Major surgery, chemotherapy, radiotherapy, or other anti-cancer therapy within 2 weeks before randomization.

• Any other malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.

• QTc interval >480 msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.

QTc (Bazett) = QT/√RR

• Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE Grade >=2, symptomatic congestive heart failure, or cerebrovascular accident excluding transient ischemic attack.

• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of palbociclib, such as history of GI surgery with may result in intestinal blind loops and patients with clinically significant gastroparesis, short bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease or diarrhea of CTCAE v4.0 Grade >1.

• Prior hematopoietic stem cell or bone marrow transplantation.

• Abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants (that cannot be safely held for biopsy) that would preclude tumor and skin biopsies.

• For fulvestrant: Ongoing anticoagulation that would preclude an IM injection

• For tamoxifen: Documented hypercoagulable state not receiving anticoagulation

• Known or possible hypersensitivity to palbociclib (CTCAE v4.0).

• Known human immunodeficiency virus infection.

• Other severe acute or chronic medical or psychiatric condition, including recent or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

• Participation in other studies involving investigational drug(s) (Phases 1-4) within 2 weeks before randomization the current study.

• Women should not become pregnant or breastfeed whilst on this study. Birth control methods are acceptable and will be discussed with study participants.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94143
2	Georgetown University	Washington	District of Columbia	United States	20007
3	University of Chicago	Chicago	Illinois	United States	60637
4	Indiana University	Indianapolis	Indiana	United States	46202
5	Johns Hopkins University	Baltimore	Maryland	United States	21287
6	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
7	University of Michigan	Ann Arbor	Michigan	United States	48109
8	Vanderbilt University	Nashville	Tennessee	United States	37240
9	Baylor College of Medicine	Houston	Texas	United States	77030

Sponsors and Collaborators

• University of California, San Francisco
• Translational Breast Cancer Research Consortium
• Dana-Farber Cancer Institute

Investigators

• Principal Investigator: Hope S Rugo, MD, University of California, San Francisco

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 1, 2017

More Information

Publications

None provided.

• Responsible Party: Hope Rugo, MD, Professor, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02384239
• Other Study ID Numbers: 147522; NCI-2015-01791
• First Posted: Mar 10, 2015
• Last Update Posted: Mar 16, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Breast Neoplasms; Tamoxifen; Fulvestrant; Palbociclib

Study Results

Participant Flow

Arm/Group Title	Palbociclib 100mg	Palbociclib 125mg
Arm/Group Description	Palbociclib dose 100mg, and either fulvestrant (500 mg intramuscular injection (IM) on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)	Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)
Period Title: Overall Study
STARTED	36	34
COMPLETED	36	34
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Palbociclib 100mg	Palbociclib 125mg	Total
Arm/Group Description	Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)	Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)	Total of all reporting groups
Overall Participants	36	34	70
Age, Customized (Count of Participants)
30-39 years old	1 2.8%	0 0%	1 1.4%
40-49 years old	5 13.9%	7 20.6%	12 17.1%
50-59 years old	11 30.6%	15 44.1%	26 37.1%
60-69 years old	12 33.3%	5 14.7%	17 24.3%
70-79 years old	5 13.9%	6 17.6%	11 15.7%
80-89 years old	2 5.6%	1 2.9%	3 4.3%
Sex: Female, Male (Count of Participants)
Female	36 100%	33 97.1%	69 98.6%
Male	0 0%	1 2.9%	1 1.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2.8%	0 0%	1 1.4%
Not Hispanic or Latino	33 91.7%	33 97.1%	66 94.3%
Unknown or Not Reported	2 5.6%	1 2.9%	3 4.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 2.8%	2 5.9%	3 4.3%
Native Hawaiian or Other Pacific Islander	0 0%	1 2.9%	1 1.4%
Black or African American	2 5.6%	1 2.9%	3 4.3%
White	28 77.8%	26 76.5%	54 77.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	5 13.9%	4 11.8%	9 12.9%
Region of Enrollment (participants) [Number]
United States	36 100%	34 100%	70 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Grade 3 or 4 Neutropenia
Description	Grade 3/4 neutropenia as defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.03 in patients with prior exposure to 1-3 lines of chemotherapy for metastatic breast cancer
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Palbociclib 100mg	Palbociclib 125mg
Arm/Group Description	Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)	Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)
Measure Participants	36	34
Number [percentage of participants]	19.4 53.9%	20.5 60.3%

2. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	PFS defined as the interval from study entry to the first documented evidence of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as at least a 20% increase in the sum of the longest diameter (SLD) of target lesions, taking as reference the smallest sum SLD recorded since the treatment started and minimum 5 mm increase over the nadir, or the appearance of one or more new lesions. Patients who remain progression-free at the time of analysis will be censored at their last date of follow-up.
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Palbociclib 100mg	Palbociclib 125mg
Arm/Group Description	Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)	Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)
Measure Participants	36	34
Median (95% Confidence Interval) [months]	6.53	9.4

3. Secondary Outcome

Title	Proportion of Participants With Demonstrated Clinical Benefit
Description	Defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) or stable disease (SD) at 24 weeks. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Two participants in the 125mg group did not have an evaluable disease assessment 24 weeks

Arm/Group Title	Palbociclib 100mg	Palbociclib 125mg
Arm/Group Description	Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)	Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)
Measure Participants	36	32
Number [proportion of participants]	0.67 1.9%	0.75 2.2%

4. Secondary Outcome

Title	Proportion of Participants With an Objective Response
Description	Defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) at 24 weeks. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Two participants in the 125mg group did not have an evaluable disease assessment 24 weeks

Arm/Group Title	Palbociclib 100mg	Palbociclib 125mg
Arm/Group Description	Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)	Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)
Measure Participants	36	32
Number [proportion of participants]	0.1111 0.3%	0.0625 0.2%

5. Secondary Outcome

Title	Median Change in Percent Positive Cells From Baseline of Ki-67
Description	Median change in percent positive cells of Ki-67 from baseline will be reported with IQR
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Palbociclib 100mg	Palbociclib 125mg
Arm/Group Description	Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)	Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)
Measure Participants	36	34
Median (Inter-Quartile Range) [change in percent positive cells]	-8	-6

6. Secondary Outcome

Title	Median Change in Percent Positive Cells From Baseline of Total-Rb
Description	Median change in percent positive cells of Total-Rb from baseline will be reported with interquartile range (IQR)
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Palbociclib 100mg	Palbociclib 125mg
Arm/Group Description	Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)	Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)
Measure Participants	36	34
Median (Inter-Quartile Range) [change in percent positive cells]	4	5

7. Secondary Outcome

Title	Median Change in Percent Positive Cells From Baseline of pS780-Rb
Description	Median change in percent positive cells of pS780-Rb from baseline will be reported with IQR
Time Frame	Up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Palbociclib 100mg	Palbociclib 125mg
Arm/Group Description	Treatment arm palbociclib dose 100mg + fulvestrant or tamoxifen	Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)
Measure Participants	36	34
Median (Inter-Quartile Range) [change in percent positive cells]	-3	-6

Adverse Events

Time Frame	Up to 24 months
Arm/Group Title	Palbociclib 100mg		Palbociclib 125mg
Arm/Group Description	Palbociclib dose 100mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)		Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)
All Cause Mortality
	Palbociclib 100mg		Palbociclib 125mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/36 (8.3%)		1/34 (2.9%)
Serious Adverse Events
	Palbociclib 100mg		Palbociclib 125mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/36 (13.9%)		2/34 (5.9%)
Gastrointestinal disorders
Gastrointestinal disorders - Other	1/36 (2.8%)	1	1/34 (2.9%)	1
Infections and infestations
Infections and infestations - Other	1/36 (2.8%)	1	0/34 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/36 (0%)	0	1/34 (2.9%)	1
Respiratory, thoracic and mediastinal disorders
Pleural effusion	2/36 (5.6%)	2	0/34 (0%)	0
Respiratory, thoracic and mediastinal disorders - Other	1/36 (2.8%)	1	0/34 (0%)	0
Other (Not Including Serious) Adverse Events
	Palbociclib 100mg		Palbociclib 125mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/36 (19.4%)		9/34 (26.5%)
Investigations
Neutrophil count decreased	5/36 (13.9%)	12	9/34 (26.5%)	19
Vascular disorders
Hypertension	2/36 (5.6%)	2	0/34 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.