Safety And Efficacy Study Of Palbociclib Plus Cetuximab Versus Cetuximab To Treat Head And Neck Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02499120
• Collaborator: (none)
• Enrollment: 124
• Locations: 71
• Arms: 2
• Anticipated Duration (Months): 84.7
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether the combination of palbociclib with cetuximab is superior to cetuximab in prolonging overall survival in HPV-negative, cetuximab-naive patients with recurrent/metastatic squamous cell carcinoma of the head and neck.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma of the Head and Neck (SCCHN)	Drug: palbociclib; Drug: Cetuximab; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 124 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A RANDOMIZED, MULTICENTER, DOUBLE-BLIND PHASE 2 STUDY OF PALBOCICLIB PLUS CETUXIMAB VERSUS CETUXIMAB FOR THE TREATMENT OF HUMAN PAPILLOMAVIRUS-NEGATIVE, CETUXIMAB-NAÏVE PATIENTS WITH RECURRENT/METASTATIC SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK AFTER FAILURE OF ONE PRIOR PLATINUM-CONTAINING CHEMOTHERAPY REGIMEN
• Actual Study Start Date: Sep 10, 2015
• Actual Primary Completion Date: Jul 19, 2018
• Anticipated Study Completion Date: Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Palbociclib plus Cetuximab Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle; in combination with Cetuximab, 400 mg/m2 initial dose as a 120-minute IV infusion followed by 250 mg/m2 weekly infused over 60 minutes.	Drug: palbociclib; Palbociclib will be supplied as capsules containing 75 mg, 100 mg, or 125 mg equivalents of palbociclib free base. Administered with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle.; Other Names: IBRANCE, PD-0332991 ; Drug: Cetuximab; Cetuximab injection for IV infusion will be provided in 100 mg/50 mL, single-use vials, and 200 mg/100 mL, single-use vials. In Japan, cetuximab will be provided in 100 mg/20 mL, single-use vials. Administered, 400 mg/m2 initial dose as a 120-minute IV infusion followed by 250 mg/m2 weekly infused over 60 minutes.; Other Names: ERBITUX
Active Comparator: Placebo plus Cetuximab Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle; in combination with Cetuximab, 400 mg/m2 initial dose as a 120-minute IV infusion followed by 250 mg/m2 weekly infused over 60 minutes.	Drug: Cetuximab; Cetuximab injection for IV infusion will be provided in 100 mg/50 mL, single-use vials, and 200 mg/100 mL, single-use vials. In Japan, cetuximab will be provided in 100 mg/20 mL, single-use vials. Administered, 400 mg/m2 initial dose as a 120-minute IV infusion followed by 250 mg/m2 weekly infused over 60 minutes.; Other Names: ERBITUX ; Drug: Placebo; Placebo for palbociclib will be indistinguishable from the palbociclib capsules and will be supplied as capsules matching in size and color the various palbociclib formulations. Administered with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle.

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [Baseline up to primary completion date (PCD) (about 34 months)]

   OS was defined as the time from the date of randomization to the date of death due to any cause. OS (in months) was calculated as (date of death - randomization date +1)/30.4. For participants lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Participants lacking survival data beyond randomization had their OS times be censored at randomization. Estimates of OS and its 95% confidence interval were determined using Kaplan-Meier method.

Secondary Outcome Measures

1. Progression Free Survival (PFS) [Baseline up to PCD (about 34 months)]

   PFS was defined as the time from the date of randomization to the date of the first documentation of objective progression of disease (PD) or death due to any cause, whichever was earlier. Estimates of the PFS curves from the Kaplan Meier method were presented.

2. Percentage of Participants With Objective Response (OR) [Baseline up to PCD (about 34 months)]

   OR was defined as the overall complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Objective response rate was defined as the proportion of participants with best overall response (BOR) of CR or PR relative to all randomized.

3. Percentage of Participants With Clinical Benefit Response (CBR) [Baseline up to PCD (about 34 months)]

   CBR was defined as the overall CR, PR, or stable disease>=24 weeks according to the RECIST version 1.1. Clinical benefit response rate was defined as the proportion of participants with CR, PR, or stable disease>= 24 weeks relative to all randomized participants and randomized participants with measurable disease at baseline.

4. Duration of Response (DR) [Baseline up to PCD (about 34 months)]

   DR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR was calculated as [the date response ended (ie, date of PD or death) - first CR or PR date + 1]/30.4.

5. Number of Participants With Treatment-Emergent Adverse Events(TEAEs) [Baseline up to PCD (about 34 months)]

   AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

6. Number of Participants With Laboratory Abnormalities [Baseline up to PCD (about 34 months)]

   The hematology, chemistry and coagulation tests were included in the laboratory examination. Hematology evaluation included hemoglobin, platelets, white blood cell, absolute neutrophils, absolute lymphocytes. Chemistry evaluation included alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose (non-fasted), albumin, phosphorus or phosphate and hemoglobin A1c (HbA1c). Coagulation evaluation included activated partial thromboplastin time/partial thromboplastin time, international normalized ratio (INR) or prothrombin time.

7. Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) [Baseline up to PCD (about 34 months)]

   The EORTC QLQ-C30 is a 30 item questionnaire composed of 5 multi-item functional subscales (physical, role, cognitive, emotional, and social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), a global health/quality of life (QOL) subscale, and 6 single items assessing other cancer related symptoms (dyspnea, sleep disturbance, appetite, diarrhea, constipation, and the financial impact of cancer). The questionnaire employed twenty-eight 4 point Likert scales with responses from "not at all" to "very much" and two 7 point Likert scales for global health and overall QOL. For functional and global QOL scales, higher scores represented a better level of functioning and all scores were converted to a 0 to 100 scale. For symptom oriented scales, a higher score represented more severe symptoms, and all scores were converted to a 0-100 scale. Negative changes from baseline indicate deterioration in functioning / global QoL scales and improvement in symptom scales.

8. Change From Baseline in European Organization for Research and Treatment of Cancer Head and Neck Module35 (EORTC QLQ-H&N35) [Baseline up to PCD (about 34 months)]

   The EORTC QLQ-H&N35 is designed to be used together with the core QLQ-C30. The recall period for the items in the module was "the past week". Items hn1 to hn30 were scored on 4 point Likert type categorical scales ("not at all", "a little", "quite a bit", "very much"). Items hn31 to hn35 had a "no/yes" response format. The scores were transformed into 0 to 100 scales, with a high score implying a high level of symptoms.Negative changes from baseline indicate deterioration in functioning / global QoL scales and improvement in symptom scales.

9. Summary of PFS and OS for P16 Negative (%Positive Tumor Cells < 70%) [Screening]

   A central test was defined as the tumor tissue-based p16 IHC test performed at a central laboratory (Ventana). The analysis of concordance between HPV status as assessed by local or central laboratory included the number and percentage of paticipants with p16 detected or not detected at the central laboratory, given that all local testing must have been negative for HPV in order for the patient to be eligible for the study. Initial analysis of the p16 status was based on the conventional cutoff of 70% p16-positive tumor cells to call out cases that might be considered HPV-positive. P16 expression was scored as positive if strong and diffuse nuclear and cytoplasmic staining was present in at least 70% of the tumor cells.

10. Summary of PFS and OS Based on Investigator Assessment by Rb Expression >= 1% [Screening]

    Rb expression in the palbociclib and cetuximab treatment group, the relationship of the biomarker (individually) with PFS and OS were explored using graphical methods such as box plots, at baseline. The tumors of participants were Rb-positive, which was defined by Rb IHC with>=1% positive tumor cells.

11. Trough Plasma Concentration (Ctrough) and Within-patient Mean Steady-state Pre-dose Concentration (WPM-Ctrough) at Steady State for Palbociblib [Pre-dose of Day 15 in Cycle 1 and Cycle 2]

    Ctrough is steady-state pre-dose concentration, which was observed directly from data. WPM-Ctrough is within-participant mean steady-state pre-dose concentration. For palbociclib, a steady-state trough was to be defined as a pre-dose plasma concentration following at least 7 consecutive days of 125 mg daily dose without dosing interruption and the time window for the PK collection was to be between 24 hr +/- 2 hr and 24 min post-dose the day prior to PK collection and no more than 1 hr post-dose on the day of PK collection.

12. Ctrough and Cendinf, WPM-Ctrough and WPM-Cendinf at Steady State for Serum Cetuximab [Pre-dose and end-of infusion of Day 15 in Cycle 1 and Cycle 2]

    Ctrough is steady-state pre-dose concentration. Cendinf is steady-state end-of-infusion concentration. Ctrough and Cendinf were observed directly from data. WPM-Ctrough and WPM-Cendinf are within-participant mean steady-state pre-dose concentration and end-of-infusion concentration. Acceptance criteria for a steady-state Cendinf was defined as a PK sample that was 1) collected after at least 3 consecutive weeks of cetuximab IV infusions without interruption or prior dose reduction and 2) was collected at the end of cetuximab infusion time +/- 10% of the actual duration of the cetuximab infusion.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Histologically or cytologically confirmed squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx, not amenable for salvage surgery or radiotherapy.

• Measurable disease as defined per RECIST v. 1.1. Tumor lesions previously irradiated or subjected to other locoregional therapy will only be deemed measureable if disease progression at the treated site after completion of therapy is clearly documented.

• HPV- negative SCCHN tumor as determined per institutional standard (eg, p16 IHC; multiplex nucleic acid sequence based amplification [NASBA] or other polymerase chain reaction [PCR]-based assays).

• Documented progressive disease according to RECIST v1.1 (Appendix 2) following receipt of at least 2 cycles of one platinum-containing chemotherapy regimen administered for R/M disease (min. 50 mg/m2 for cisplatin, minimum area under the curve [AUC] > 4 for carboplatin).

• Availability of a tumor tissue specimen (ie, archived formalin fixed paraffin embedded tissue [block preferred, or 15 unstained slides]), which will be used for centralized, retrospective biomarker analysis. If archived tumor tissue is not available, then a de novo biopsy will be required for patient participation.

Key Exclusion Criteria:

• Prior nasopharyngeal cancer, salivary gland or sinus tumors.

• More than one chemotherapeutic regimen given for R/M disease. Prior treatment with immunotherapy is allowed.

• 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 with local therapy (eg, radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization.

• Progressive disease within 3 months after completion of curatively intended treatment for locoregionally advanced SCCHN.

• Difficulty swallowing capsules.

• Prior use of cetuximab in the R/M disease treatment setting (except cetuximab during curative radiotherapy)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UC San Diego Medical Center - La Jolla (Thornton Hospital)	La Jolla	California	United States	92037
2	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
3	UC San Diego Medical Center- Hillcrest	San Diego	California	United States	92103
4	University Medical Center, lnc.:DBA University of Louisville Hospital	Louisville	Kentucky	United States	40202
5	Mayo Clinic	Rochester	Minnesota	United States	55905
6	Siteman Cancer Center - West County	Creve Coeur	Missouri	United States	63141
7	Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
8	Washington University School of Medicine, Siteman Cancer Center	Saint Louis	Missouri	United States	63110
9	Siteman Cancer Center - South County	Saint Louis	Missouri	United States	63129
10	Siteman Cancer Center	Saint Peters	Missouri	United States	63376
11	University of Cincinnati Investigational Pharmacy	Cincinnati	Ohio	United States	45219
12	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45219
13	UC Health Physicians Office South	West Chester	Ohio	United States	45069
14	Henry Joyce Cancer Clinic	Nashville	Tennessee	United States	37232
15	Fakultni nemocnice Olomouc	Olomouc		Czechia	775 20
16	Fakultni nemocnice Olomouc, Lekarna	Olomouc		Czechia	77520
17	Nemocnice Na Bulovce, Centralni laboratore Pavilon c. 8	Praha 8		Czechia	180 81
18	Nemocnice Na Bulovce, Lekarna, Oddeleni Centralni pripravy	Praha 8		Czechia	180 81
19	Nemocnice Na Bulovce, Ustav radiacni onkologie	Praha 8		Czechia	180 81
20	Debreceni Egyetem klinikai Koezpont Onkologiai Intezet	Debrecen		Hungary	4032
21	Neuro CT Kft	Pecs		Hungary	7623
22	Pecsi Tudomanyegyetem, Klinikai Kozpont, Laboratoriumi	Pecs		Hungary	7624
23	Pecsi Tudomanyegyetem, Klinikai Kozpont,	Pecs		Hungary	7624
24	Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet,Onkologiai Kozpont	Szolnok		Hungary	5000
25	Istituto Nazionale Tumori Napoli	Napoli		Italy	80131
26	Aichi cancer center Central hospital	Nagoya	Aichi	Japan	464-8681
27	National Cancer Center Hospital East	Kashiwa	Chiba	Japan	277-8577
28	Hokkaido University Hospital/Otolaryngology	Sapporo	Hokkaido	Japan	060-8648
29	Shizuoka Cancer Center	Sunto-gun	Shizuoka	Japan	411-8777
30	Seoul National University Hospital	Seoul		Korea, Republic of	03080
31	Asan Medical Center	Seoul		Korea, Republic of	05505
32	Samsung Medical Center	Seoul		Korea, Republic of	06351
33	Instituto Nacional de Cancerologia	Mexico	Distrito Federal	Mexico	14080
34	Hospital Universitario Dr. Jose Eleuterio Gonzalez	Monterrey	Nuevo LEON	Mexico	64460
35	Cirugia y Ginecobstetricia de Oaxaca S.A de C.V Hospital Reforma	Oaxaca	Oaxaca DE Juarez	Mexico	68000
36	Diaz San Juan Noe, Imagenologia Siglo XXI San Felipe	Oaxaca	Oaxaca DE Juarez	Mexico	68020
37	Daniel Javier Mendez Lopez Imagen y Diagnostico Medico IDM	Oaxaca	Oaxaca DE Juarez	Mexico	68120
38	Oaxaca Site Management Organization S C	Oaxaca		Mexico	68000
39	Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. ks. B. Markiewicza	Brzozow		Poland	36200
40	Uniwersyteckie Centrum Kliniczne Klinika Onkologii i Radioterapii	Gdansk		Poland	80-211
41	Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi Oddzial Chemioterapii	Lodz		Poland	93-513
42	SPZOZ MSWiA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie Oddzial Kliniczny Onkologii	Olsztyn		Poland	10-228
43	SC Medisprof SRL	Cluj-Napoca	Cluj	Romania	400058
44	Centrul de Oncologie Sf. Nectarie SRL	Craiova	Dolj	Romania	200347
45	SC Oncolab SRL	Craiova	Dolj	Romania	200385
46	S.C. ONCOCENTER Oncologie Clinica S.R.L.	Timisoara	Timis	Romania	300166
47	Spitalul Clinic Judetean de Urgenta Sibiu, Clinica Oncologie Medicala	Sibiu		Romania	550245
48	State Budgetary Healthcare Institution of Arkhangelsk Region	Arkhangelsk	Arkhangelsk Region	Russian Federation	163045
49	State Budgetary Healthcare Institution "Oncology Center #2" of the Ministry of	Sochi	Krasnodar Region	Russian Federation	354057
50	State Autonomous Healthcare Institution Republican Clinical Oncology Dispensary of the Ministry	Kazan	Tatarstan Republic	Russian Federation	420029
51	FSBI "National Medical Scientific Centre of Oncology n.a.N.N.Petrov" of the MOH of Russia	Saint-Petersburg		Russian Federation	197758
52	Institute for Oncology and Radiology of Serbia	Belgrade		Serbia	11000
53	Military Medical Academy	Belgrade		Serbia	11000
54	Narodny onkologicky ustav	Bratislava		Slovakia	83310
55	POKO Poprad, s.r.o.	Poprad		Slovakia	05801
56	Servicio de Oncologia	Pamplona	Navarra	Spain	31008
57	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
58	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
59	Taichung Veterans General Hospital	Taichung City		Taiwan	407
60	China Medical University Hospital	Taichung		Taiwan	40447
61	National Cheng Kung University Hospital	Tainan		Taiwan	70154
62	National Cheng Kung University Hospital Department of Pathology	Tainan		Taiwan	704
63	Tri-Service General Hospital	Taipei		Taiwan	114
64	Communal Institution of Kherson Regional Council Kherson Regional Oncological Dispensary	Antonivka	Kherson Region	Ukraine	73000
65	Communal Institution "Chernivtsi Regional clinical oncology dispensary",	Chernivtsy		Ukraine	58013
66	SI Dnipropetrovsk Medical Academy of MoH of Ukraine, Chair of Oncology and Medical Radiology	Dnipropetrovsk		Ukraine	49044
67	CI Dnipropetrovsk City Multifunctional Clinical Hospital #4 of Dnipropetrovsk Regional Council	Dnipropetrovsk		Ukraine	49102
68	Regional Clinical Hospital, Department of microsurgery of otolaryngology organs	Ivano-Frankivsk		Ukraine	76018
69	Communal Institution "Krivorizhskiy Oncology Dispensary" of Dnipropetrovsk Regional Council,	Kriviy Rig		Ukraine	50048
70	Clinic of SI "Institute of Otolaryngology n.a. Prof. O.S. Kolomyichenka of NAMSU"	Kyiv		Ukraine	03057
71	Podilskiy Regional Center of Oncology, Chemotherapy Department	Vinnytsia		Ukraine	21029

Sponsors and Collaborators

• Pfizer

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Mar 31, 2016
• Statistical Analysis Plan - Apr 26, 2018

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: NCT02499120
• Other Study ID Numbers: A5481044; 2015-000515-41; PALATINUS
• First Posted: Jul 15, 2015
• Last Update Posted: Jul 12, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Pfizer: palbociclib, cetuximab, human papillomavirus, squamous cell carcinoma, head and neck cancer
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Cetuximab; Palbociclib

Study Results

Participant Flow

Pre-assignment Detail	A total of 125 participants were randomized; among them, 124 participants received study treatments. One (1) participant in the palbociclib + cetuximab treatment group was randomized but not treated. Data reported is based on the primary analysis date of 19 July 2018.

Arm/Group Title	Palbociclib + Cetuximab	Placebo + Cetuximab
Arm/Group Description	Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.	Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Period Title: Overall Study
STARTED	65	60
Received Treatment	64	60
COMPLETED	0	0
NOT COMPLETED	65	60

Baseline Characteristics

Arm/Group Title	Palbociclib + Cetuximab	Placebo + Cetuximab	Total
Arm/Group Description	Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.	Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.	Total of all reporting groups
Overall Participants	65	60	125
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.3 (10.2)	60.9 (10.1)	59.5 (10.2)
Sex: Female, Male (Count of Participants)
Female	8 12.3%	4 6.7%	12 9.6%
Male	57 87.7%	56 93.3%	113 90.4%
Race/Ethnicity, Customized (Count of Participants)
White	47 72.3%	46 76.7%	93 74.4%
Black	1 1.5%	1 1.7%	2 1.6%
Asian	15 23.1%	13 21.7%	28 22.4%
Other	2 3.1%	0 0%	2 1.6%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from the date of randomization to the date of death due to any cause. OS (in months) was calculated as (date of death - randomization date +1)/30.4. For participants lacking survival data beyond the date of their last follow-up, the OS time was censored on the last date they were known to be alive. Participants lacking survival data beyond randomization had their OS times be censored at randomization. Estimates of OS and its 95% confidence interval were determined using Kaplan-Meier method.
Time Frame	Baseline up to primary completion date (PCD) (about 34 months)

Outcome Measure Data

Analysis Population Description

The analysis population was intent-to-treat (ITT) population, which included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Palbociclib + Cetuximab	Placebo + Cetuximab
Arm/Group Description	Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.	Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Measure Participants	65	60
Median (95% Confidence Interval) [months]	9.7	7.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Palbociclib + Cetuximab, Placebo + Cetuximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1800
	Comments	1-sided p-value was from the log-rank test stratified by stratification factors ECOG(Eastern Cooperative Oncology Group) per randomization.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.820
	Confidence Interval	(2-Sided) 95%; 0.536 to 1.253
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS was defined as the time from the date of randomization to the date of the first documentation of objective progression of disease (PD) or death due to any cause, whichever was earlier. Estimates of the PFS curves from the Kaplan Meier method were presented.
Time Frame	Baseline up to PCD (about 34 months)

Outcome Measure Data

Analysis Population Description

The analysis population was intent-to-treat (ITT) population, which included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Palbociclib + Cetuximab	Placebo + Cetuximab
Arm/Group Description	Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.	Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Measure Participants	65	60
Median (95% Confidence Interval) [months]	3.9	4.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Palbociclib + Cetuximab, Placebo + Cetuximab
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4953
	Comments	1-sided p-value was from the log-rank test stratified by stratification factors ECOG per randomization.
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.000
	Confidence Interval	(2-Sided) 95%; 0.669 to 1.495
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Objective Response (OR)
Description	OR was defined as the overall complete response (CR) or partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Objective response rate was defined as the proportion of participants with best overall response (BOR) of CR or PR relative to all randomized.
Time Frame	Baseline up to PCD (about 34 months)

Outcome Measure Data

Analysis Population Description

The analysis population was ITT population, which included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Palbociclib + Cetuximab	Placebo + Cetuximab
Arm/Group Description	Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.	Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Measure Participants	65	60
Number (95% Confidence Interval) [Percentage of participants]	27.7 42.6%	25.0 41.7%

4. Secondary Outcome

Title	Percentage of Participants With Clinical Benefit Response (CBR)
Description	CBR was defined as the overall CR, PR, or stable disease>=24 weeks according to the RECIST version 1.1. Clinical benefit response rate was defined as the proportion of participants with CR, PR, or stable disease>= 24 weeks relative to all randomized participants and randomized participants with measurable disease at baseline.
Time Frame	Baseline up to PCD (about 34 months)

Outcome Measure Data

Analysis Population Description

The analysis population was ITT population, which included all participants who were randomized, with study drug assignment designated according to initial randomization, regardless of whether participants received study drug or received a different drug from that to which they were randomized.

Arm/Group Title	Palbociclib + Cetuximab	Placebo + Cetuximab
Arm/Group Description	Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.	Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Measure Participants	65	60
Number (95% Confidence Interval) [Percentage of participants]	36.9 56.8%	36.7 61.2%

5. Secondary Outcome

Title	Duration of Response (DR)
Description	DR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR was calculated as [the date response ended (ie, date of PD or death) - first CR or PR date + 1]/30.4.
Time Frame	Baseline up to PCD (about 34 months)

Outcome Measure Data

Analysis Population Description

DR was only calculated for the subgroup of all ITT participants with an objective tumor response.

Arm/Group Title	Palbociclib + Cetuximab	Placebo + Cetuximab
Arm/Group Description	Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.	Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Measure Participants	18	15
Median (95% Confidence Interval) [months]	7.6	7.4

6. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events(TEAEs)
Description	AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Time Frame	Baseline up to PCD (about 34 months)

Outcome Measure Data

Analysis Population Description

The analysis population included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received.

Arm/Group Title	Palbociclib + Cetuximab	Placebo + Cetuximab
Arm/Group Description	Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.	Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Measure Participants	64	60
AEs (all causality)	60 92.3%	56 93.3%
AEs (treatment-related)	57 87.7%	47 78.3%
SAEs (all causality)	25 38.5%	19 31.7%
SAEs (treatment-related)	7 10.8%	2 3.3%
Grade 3 or 4 AEs (all causality)	33 50.8%	18 30%
Grade 5 AEs (all causality)	15 23.1%	11 18.3%
Grade 3 or 4 AEs (treatment-related)	34 52.3%	9 15%
Grade 5 AEs (treatment-related)	1 1.5%	0 0%

7. Secondary Outcome

Title	Number of Participants With Laboratory Abnormalities
Description	The hematology, chemistry and coagulation tests were included in the laboratory examination. Hematology evaluation included hemoglobin, platelets, white blood cell, absolute neutrophils, absolute lymphocytes. Chemistry evaluation included alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, sodium, potassium, magnesium, chloride, total calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose (non-fasted), albumin, phosphorus or phosphate and hemoglobin A1c (HbA1c). Coagulation evaluation included activated partial thromboplastin time/partial thromboplastin time, international normalized ratio (INR) or prothrombin time.
Time Frame	Baseline up to PCD (about 34 months)

Outcome Measure Data

Analysis Population Description

The analysis population included all participants with at least 1 observation of the laboratory test while on study treatment or during lag time.

Arm/Group Title	Palbociclib + Cetuximab	Placebo + Cetuximab
Arm/Group Description	Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.	Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Measure Participants	62	59
Count of Participants [Participants]	61 93.8%	55 91.7%

8. Secondary Outcome

Title	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)
Description	The EORTC QLQ-C30 is a 30 item questionnaire composed of 5 multi-item functional subscales (physical, role, cognitive, emotional, and social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), a global health/quality of life (QOL) subscale, and 6 single items assessing other cancer related symptoms (dyspnea, sleep disturbance, appetite, diarrhea, constipation, and the financial impact of cancer). The questionnaire employed twenty-eight 4 point Likert scales with responses from "not at all" to "very much" and two 7 point Likert scales for global health and overall QOL. For functional and global QOL scales, higher scores represented a better level of functioning and all scores were converted to a 0 to 100 scale. For symptom oriented scales, a higher score represented more severe symptoms, and all scores were converted to a 0-100 scale. Negative changes from baseline indicate deterioration in functioning / global QoL scales and improvement in symptom scales.
Time Frame	Baseline up to PCD (about 34 months)

Outcome Measure Data

Analysis Population Description

The analysis population included all ITT participants, who had both baseline and at least 1 follow-up patient reported outcome (PRO) assessment before treatment discontinuation.

Arm/Group Title	Palbociclib + Cetuximab	Placebo + Cetuximab
Arm/Group Description	Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.	Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Measure Participants	57	55
Global health status / QOL	2.82	2.69
Functional scale: Physical functioning	0.74	-0.46
Functional scale: Role functioning	-0.41	-1.60
Functional scale: Emotional functioning	4.16	3.56
Functional scale: Cognitive functioning	-1.47	-1.23
Functional scale: Social functioning	1.24	2.08
Symptom scale/item: Fatigue	-2.79	-5.12
Symptom scale/item: Nausea and vomiting	-0.87	-1.04
Symptom scale/item: Pain	-5.98	-6.10
Symptom scale/item: Dyspnoea	3.07	5.09
Symptom scale/item: Insomnia	-4.62	-5.02
Symptom scale/item: Appetite loss	2.25	-0.69
Symptom scale/item: Constipation	-4.12	-1.33
Symptom scale/item: Diarrhoea	4.26	1.74
Symptom scale/item: Financial difficulties	-5.26	-0.27

9. Secondary Outcome

Title	Change From Baseline in European Organization for Research and Treatment of Cancer Head and Neck Module35 (EORTC QLQ-H&N35)
Description	The EORTC QLQ-H&N35 is designed to be used together with the core QLQ-C30. The recall period for the items in the module was "the past week". Items hn1 to hn30 were scored on 4 point Likert type categorical scales ("not at all", "a little", "quite a bit", "very much"). Items hn31 to hn35 had a "no/yes" response format. The scores were transformed into 0 to 100 scales, with a high score implying a high level of symptoms.Negative changes from baseline indicate deterioration in functioning / global QoL scales and improvement in symptom scales.
Time Frame	Baseline up to PCD (about 34 months)

Outcome Measure Data

Analysis Population Description

The analysis population included all ITT participants, who had both baseline and at least 1 follow-up PRO assessment before treatment discontinuation.

Arm/Group Title	Palbociclib + Cetuximab	Placebo + Cetuximab
Arm/Group Description	Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.	Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Measure Participants	57	55
Symptom scale/item: Pain	-3.57	-0.41
Symptom scale/item: Swallowing	-4.34	-1.47
Symptom scale/item: Senses problems	-1.58	-1.88
Symptom scale/item: Speech problems	-4.54	-2.69
Symptom scale/item: Trouble with social eating	-5.55	-0.71
Symptom scale/item: Trouble with social contact	-1.27	3.45
Symptom scale/item: Less sexuality	-3.32	4.90
Symptom scale/item: Teeth	-1.59	-1.88
Symptom scale/item: Opening mouth	0.35	0.22
Symptom scale/item: Dry mouth	-6.30	3.44
Symptom scale/item: Sticky saliva	-3.91	4.68
Symptom scale/item: Coughing	-3.99	-1.72
Symptom scale/item: Felt ill	1.320	0.12
Symptom scale/item: Pain killers	-13.18	-11.39
Symptom scale/item: Nutritional supplements	0.351	-4.37
Symptom scale/item: Feeding tube	-6.36	-0.11
Symptom scale/item: Weight loss	-17.72	-9.47
Symptom scale/item: Weight gain	-3.03	5.16

10. Secondary Outcome

Title	Summary of PFS and OS for P16 Negative (%Positive Tumor Cells < 70%)
Description	A central test was defined as the tumor tissue-based p16 IHC test performed at a central laboratory (Ventana). The analysis of concordance between HPV status as assessed by local or central laboratory included the number and percentage of paticipants with p16 detected or not detected at the central laboratory, given that all local testing must have been negative for HPV in order for the patient to be eligible for the study. Initial analysis of the p16 status was based on the conventional cutoff of 70% p16-positive tumor cells to call out cases that might be considered HPV-positive. P16 expression was scored as positive if strong and diffuse nuclear and cytoplasmic staining was present in at least 70% of the tumor cells.
Time Frame	Screening

Outcome Measure Data

Analysis Population Description

The analysis population included all participants treated with cetuximab in combination with placebo or palbociclib who had at least 1 baseline biomarker assessment.

Arm/Group Title	Palbociclib + Cetuximab	Placebo + Cetuximab
Arm/Group Description	Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.	Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Measure Participants	54	48
PFS	3.7	5.0
OS	9.9	8.0

11. Secondary Outcome

Title	Summary of PFS and OS Based on Investigator Assessment by Rb Expression >= 1%
Description	Rb expression in the palbociclib and cetuximab treatment group, the relationship of the biomarker (individually) with PFS and OS were explored using graphical methods such as box plots, at baseline. The tumors of participants were Rb-positive, which was defined by Rb IHC with>=1% positive tumor cells.
Time Frame	Screening

Outcome Measure Data

Analysis Population Description

The analysis population included all participants treated with cetuximab in combination with placebo or palbociclib who had at least 1 baseline biomarker assessment.

Arm/Group Title	Palbociclib + Cetuximab	Placebo + Cetuximab
Arm/Group Description	Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.	Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Measure Participants	57	53
PFS	3.9	4.6
OS	10.5	7.8

12. Secondary Outcome

Title	Trough Plasma Concentration (Ctrough) and Within-patient Mean Steady-state Pre-dose Concentration (WPM-Ctrough) at Steady State for Palbociblib
Description	Ctrough is steady-state pre-dose concentration, which was observed directly from data. WPM-Ctrough is within-participant mean steady-state pre-dose concentration. For palbociclib, a steady-state trough was to be defined as a pre-dose plasma concentration following at least 7 consecutive days of 125 mg daily dose without dosing interruption and the time window for the PK collection was to be between 24 hr +/- 2 hr and 24 min post-dose the day prior to PK collection and no more than 1 hr post-dose on the day of PK collection.
Time Frame	Pre-dose of Day 15 in Cycle 1 and Cycle 2

Outcome Measure Data

Analysis Population Description

The analysis population included all as-treated participants, who were treated with the study treatments and had at least measured plasma concentration for at least 1 analyte (palbociclib and/or cetuximab)

Arm/Group Title	Palbociclib + Cetuximab
Arm/Group Description	Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Measure Participants	57
Ctrough Cycle 1 Day 15	69.8 (28.208)
Ctrough Cycle 2 Day 15	67.8 (28.905)
WPM-Ctrough	71.6 (30.183)

13. Secondary Outcome

Title	Ctrough and Cendinf, WPM-Ctrough and WPM-Cendinf at Steady State for Serum Cetuximab
Description	Ctrough is steady-state pre-dose concentration. Cendinf is steady-state end-of-infusion concentration. Ctrough and Cendinf were observed directly from data. WPM-Ctrough and WPM-Cendinf are within-participant mean steady-state pre-dose concentration and end-of-infusion concentration. Acceptance criteria for a steady-state Cendinf was defined as a PK sample that was 1) collected after at least 3 consecutive weeks of cetuximab IV infusions without interruption or prior dose reduction and 2) was collected at the end of cetuximab infusion time +/- 10% of the actual duration of the cetuximab infusion.
Time Frame	Pre-dose and end-of infusion of Day 15 in Cycle 1 and Cycle 2

Outcome Measure Data

Analysis Population Description

The analysis population included all as-treated participants, who were treated with the study treatments and had at least measured plasma concentration for at least 1 analyte (palbociclib and/or cetuximab)

Arm/Group Title	Palbociclib + Cetuximab	Placebo + Cetuximab
Arm/Group Description	Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.	Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
Measure Participants	57	57
Ctrough Cycle 1 Day 15	39706.4 (92)	42914.1 (62)
Ctrough Cycle 2 Day 15	51005.3 (74)	52995.7 (71)
WPM-Ctrough	45605.9 (83)	46796.5 (63)
Cendinf Cycle 1 Day 15	145748.3 (43)	137185.5 (61)
Cendinf Cycle 2 Day 15	149155.7 (38)	153310.1 (39)
WPM-Cendinf	149119.2 (36)	148063.3 (39)

Adverse Events

Time Frame	Baseline up to PCD (about 34 months) ( All-cause mortality included all death from start of treatment to the follow-up period occurring greater than 28 days after last dose)
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. 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. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
Arm/Group Title	Palbociclib + Cetuximab		Placebo + Cetuximab
Arm/Group Description	Participants received Palbociclib, 125 mg, orally once daily (QD) with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute intravenous (IV) infusion followed by 250 mg/m^2 weekly infused over 60 minutes.		Participants received Placebo orally QD with food on Day 1 to Day 21 followed by 7 days off treatment in a 28-day cycle in combination with Cetuximab, 400 mg/m^2 initial dose as a 120-minute IV infusion followed by 250 mg/m^2 weekly infused over 60 minutes.
All Cause Mortality
	Palbociclib + Cetuximab		Placebo + Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/64 (70.3%)		42/60 (70%)
Serious Adverse Events
	Palbociclib + Cetuximab		Placebo + Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/64 (39.1%)		19/60 (31.7%)
Blood and lymphatic system disorders
Anaemia	0/64 (0%)		1/60 (1.7%)
Febrile neutropenia	2/64 (3.1%)		0/60 (0%)
Neutropenia	1/64 (1.6%)		0/60 (0%)
Cardiac disorders
Cardiac arrest	1/64 (1.6%)		0/60 (0%)
Cardio-respiratory arrest	1/64 (1.6%)		0/60 (0%)
Gastrointestinal disorders
Duodenal ulcer haemorrhage	0/64 (0%)		1/60 (1.7%)
Dysphagia	0/64 (0%)		1/60 (1.7%)
Large intestine perforation	1/64 (1.6%)		0/60 (0%)
Mouth haemorrhage	1/64 (1.6%)		0/60 (0%)
Nausea	0/64 (0%)		1/60 (1.7%)
General disorders
Death	1/64 (1.6%)		0/60 (0%)
Disease progression	7/64 (10.9%)		6/60 (10%)
General physical health deterioration	1/64 (1.6%)		0/60 (0%)
Pyrexia	1/64 (1.6%)		0/60 (0%)
Immune system disorders
Anaphylactic reaction	0/64 (0%)		1/60 (1.7%)
Infections and infestations
Abscess	0/64 (0%)		1/60 (1.7%)
Lung abscess	1/64 (1.6%)		0/60 (0%)
Pneumonia	4/64 (6.3%)		0/60 (0%)
Pneumonia bacterial	0/64 (0%)		1/60 (1.7%)
Pulmonary tuberculosis	0/64 (0%)		1/60 (1.7%)
Sepsis	0/64 (0%)		2/60 (3.3%)
Injury, poisoning and procedural complications
Femoral neck fracture	1/64 (1.6%)		0/60 (0%)
Hip fracture	0/64 (0%)		1/60 (1.7%)
Infusion related reaction	1/64 (1.6%)		0/60 (0%)
Investigations
Neutrophil count decreased	1/64 (1.6%)		0/60 (0%)
Metabolism and nutrition disorders
Dehydration	1/64 (1.6%)		0/60 (0%)
Hypoalbuminaemia	0/64 (0%)		1/60 (1.7%)
Musculoskeletal and connective tissue disorders
Back pain	0/64 (0%)		1/60 (1.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage	1/64 (1.6%)		1/60 (1.7%)
Nervous system disorders
Coma	1/64 (1.6%)		0/60 (0%)
Seizure	1/64 (1.6%)		1/60 (1.7%)
Respiratory, thoracic and mediastinal disorders
Laryngeal obstruction	1/64 (1.6%)		0/60 (0%)
Pneumonia aspiration	1/64 (1.6%)		0/60 (0%)
Pneumonitis	1/64 (1.6%)		1/60 (1.7%)
Pneumothorax	0/64 (0%)		1/60 (1.7%)
Pulmonary embolism	1/64 (1.6%)		2/60 (3.3%)
Pulmonary haemorrhage	1/64 (1.6%)		1/60 (1.7%)
Respiratory failure	1/64 (1.6%)		0/60 (0%)
Other (Not Including Serious) Adverse Events
	Palbociclib + Cetuximab		Placebo + Cetuximab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	54/64 (84.4%)		53/60 (88.3%)
Blood and lymphatic system disorders
Anaemia	23/64 (35.9%)		8/60 (13.3%)
Leukopenia	13/64 (20.3%)		0/60 (0%)
Lymphopenia	7/64 (10.9%)		1/60 (1.7%)
Neutropenia	18/64 (28.1%)		0/60 (0%)
Thrombocytopenia	5/64 (7.8%)		0/60 (0%)
Gastrointestinal disorders
Constipation	7/64 (10.9%)		5/60 (8.3%)
Diarrhoea	9/64 (14.1%)		5/60 (8.3%)
Dysphagia	9/64 (14.1%)		5/60 (8.3%)
Nausea	8/64 (12.5%)		6/60 (10%)
Stomatitis	4/64 (6.3%)		0/60 (0%)
Vomiting	4/64 (6.3%)		1/60 (1.7%)
General disorders
Asthenia	5/64 (7.8%)		7/60 (11.7%)
Fatigue	8/64 (12.5%)		8/60 (13.3%)
Pyrexia	9/64 (14.1%)		7/60 (11.7%)
Infections and infestations
Paronychia	2/64 (3.1%)		6/60 (10%)
Pneumonia	4/64 (6.3%)		5/60 (8.3%)
Investigations
Alanine aminotransferase increased	1/64 (1.6%)		5/60 (8.3%)
Aspartate aminotransferase increased	2/64 (3.1%)		4/60 (6.7%)
Blood creatinine increased	5/64 (7.8%)		3/60 (5%)
Neutrophil count decreased	9/64 (14.1%)		0/60 (0%)
Platelet count decreased	10/64 (15.6%)		0/60 (0%)
Weight decreased	5/64 (7.8%)		3/60 (5%)
White blood cell count decreased	11/64 (17.2%)		0/60 (0%)
Metabolism and nutrition disorders
Decreased appetite	12/64 (18.8%)		9/60 (15%)
Hyperglycaemia	3/64 (4.7%)		5/60 (8.3%)
Hypoalbuminaemia	0/64 (0%)		4/60 (6.7%)
Hypocalcaemia	6/64 (9.4%)		1/60 (1.7%)
Hypokalaemia	6/64 (9.4%)		1/60 (1.7%)
Hypomagnesaemia	11/64 (17.2%)		7/60 (11.7%)
Hyponatraemia	4/64 (6.3%)		5/60 (8.3%)
Musculoskeletal and connective tissue disorders
Neck pain	5/64 (7.8%)		3/60 (5%)
Nervous system disorders
Dizziness	2/64 (3.1%)		6/60 (10%)
Headache	5/64 (7.8%)		4/60 (6.7%)
Respiratory, thoracic and mediastinal disorders
Cough	2/64 (3.1%)		5/60 (8.3%)
Dyspnoea	4/64 (6.3%)		8/60 (13.3%)
Productive cough	6/64 (9.4%)		4/60 (6.7%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform	14/64 (21.9%)		13/60 (21.7%)
Dry skin	9/64 (14.1%)		3/60 (5%)
Pruritus	7/64 (10.9%)		4/60 (6.7%)
Rash	27/64 (42.2%)		21/60 (35%)
Vascular disorders
Hypertension	4/64 (6.3%)		2/60 (3.3%)
Hypotension	3/64 (4.7%)		4/60 (6.7%)

Limitations/Caveats

The study is still ongoing. This report reflects data collected up to 19 July 2018, and will be updated after completion of the whole study.

More Information

Certain Agreements

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.