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A Study of Palbociclib (PD-0332991) + Letrozole vs. Letrozole For 1st Line Treatment Of Postmenopausal Women With ER+/HER2- Advanced Breast Cancer (PALOMA-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01740427
Recruitment Status : Active, not recruiting
First Posted : December 4, 2012
Results First Posted : April 26, 2017
Last Update Posted : February 24, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Breast Neoplasms
Interventions Drug: PD-0332991
Drug: Letrozole
Drug: Placebo
Enrollment 666
Recruitment Details Between 28 February 2013 and 29 July 2014, 666 women were randomized at 186 sites in 17 countries.
Pre-assignment Details The study consisted of a screening visit within 28 days before randomization, an active treatment phase, divided in cycles of 28 days each, and a post-treatment follow-up period during which survival and new anti-cancer therapy information was collected every 6 months (±7 days) from the last dose of study treatment.
Arm/Group Title Palbociclib Plus Letrozole Placebo Plus Letrozole
Hide Arm/Group Description Participants received letrozole 2.5 milligram (mg) orally QD (once daily) combined with palbociclib 125 mg QD for 21 days of every-28-day cycle, followed by 7 days off treatment. Participants received letrozole 2.5 mg orally QD combined with placebo QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Period Title: Overall Study
Started 444 222
Completed 0 0
Not Completed 444 222
Reason Not Completed
Ongoing at date of cutoff (26 Feb 2016)             205             61
Objective progression or relapse             172             125
Adverse Event             20             9
Global deterioration of health status             16             9
Subject refused continued treatment             12             9
Unspecified reasons             6             4
Death             6             2
Protocol Violation             5             3
Lost to Follow-up             1             0
Study terminated by Sponsor             1             0
Arm/Group Title Palbociclib Plus Letrozole Placebo Plus Letrozole Total
Hide Arm/Group Description Participants received letrozole 2.5 milligram (mg) orally QD (once daily) combined with palbociclib 125 mg QD for 21 days of every-28-day cycle, followed by 7 days off treatment. Participants received letrozole 2.5 mg orally QD combined with placebo QD for 21 days of every-28-day cycle, followed by 7 days off treatment. Total of all reporting groups
Overall Number of Baseline Participants 444 222 666
Hide Baseline Analysis Population Description
The intent-to-treat (ITT) population 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.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 444 participants 222 participants 666 participants
61.7  (10.6) 60.6  (11.2) 61.3  (10.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 444 participants 222 participants 666 participants
Female
444
 100.0%
222
 100.0%
666
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Progression-Free Survival (PFS) as Assessed by the Investigator.
Hide Description PFS is defined as the time from the date of randomization to the date of the first documentation of objective tumor progression as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) or death due to any cause in the absence of documented PD, whichever occurs first. If tumor progression data include more than 1 date, the first date will be used. PFS (in months) will be calculated as (first event date − randomization date +1)/30.4. Progression is defined using RECIST v1.1, as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions, or the appearance of new lesions.
Time Frame From randomization date to date of first documentation of progression OR death (up to approximately 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population or full analysis set included all participants who were randomized, with study medication, regardless of whether participants received study medication or received a different drug from that to which they were randomized.
Arm/Group Title Palbociclib Plus Letrozole Placebo Plus Letrozole
Hide Arm/Group Description:
Participants received letrozole 2.5 milligram (mg) orally QD (once daily) combined with palbociclib 125 mg QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Participants received letrozole 2.5 mg orally QD combined with placebo QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Overall Number of Participants Analyzed 444 222
Median (95% Confidence Interval)
Unit of Measure: Months
24.8 [1] 
(22.1 to NA)
14.5
(12.9 to 17.1)
[1]
The value was not available because there was not enough disease progression events in the treatment group at the time of analysis, due to drug benefit.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.000001
Comments 1-sided p-value from the stratified log-rank test.
Method Stratified Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.576
Confidence Interval (2-Sided) 95%
0.463 to 0.718
Estimation Comments Assuming proportional hazards, a hazard ratio of less than 1 indicates a risk reduction in favor of palbociclib plus letrozole.
2.Secondary Outcome
Title Objective Response as Assessed by the Investigator
Hide Description Objective Response (OR) is defined as the overall complete response (CR) or partial response (PR) according to the RECIST v1.1. Objective Response Rate (ORR) is defined as proportion of patients with CR or PR relative to all randomized patients with measurable disease at baseline. Patients who do not have on-study radiographic tumor re-evaluation, who received anti-tumor treatment, or who died, progressed/ dropped out for any reason prior to reaching a CR or PR were counted as non-responders in the assessment of ORR. Per RECIST v1.1, CR: Complete disappearance of target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis <10mm). PR: ≥30% decrease under baseline of the sum of diameters of all target measurable lesions.The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. Stable Disease: neither sufficient shrinkage nor increase to qualify for disease progression.
Time Frame From randomization until end of treatment (up to approximately 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population or full analysis set included all participants who were randomized, with study medication, regardless of whether participants received study medication or received a different drug from that to which they were randomized.
Arm/Group Title Palbociclib Plus Letrozole Placebo Plus Letrozole
Hide Arm/Group Description:
Participants received letrozole 2.5 milligram (mg) orally QD (once daily) combined with palbociclib 125 mg QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Participants received letrozole 2.5 mg orally QD combined with placebo QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Overall Number of Participants Analyzed 444 222
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
46.4
(41.7 to 51.2)
38.3
(31.9 to 45.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments Stratified analysis: Stratified by disease site (visceral vs non-visceral) per randomization.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0224
Comments 1-sided p-value is from exact test.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.428
Confidence Interval (2-Sided) 95%
1.008 to 2.030
Estimation Comments An Odds Ratio >1 means better response in favor of the palbociclib plus letrozole arm.
3.Secondary Outcome
Title Objective Response: Patients With Measurable Disease at Baseline as Assessed by the Investigator
Hide Description The OR is defined as the overall CR or PR according to the RECIST v1.1. ORR is defined as proportion of patients with CR or PR relative to all randomized patients with measurable disease at baseline. Patients who do not have on-study radiographic tumor re-evaluation, who received anti-tumor treatment, or who died, progressed/ dropped out for any reason prior to reaching a CR or PR were counted as non-responders in the assessment of ORR. Per RECIST v1.1, CR: Complete disappearance of target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis <10mm). PR: ≥30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. Stable Disease: neither sufficient shrinkage nor increase to qualify for disease progression.
Time Frame From randomization until end of treatment (up to approximately 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who had measurable disease at baseline. A total of 338 and 171 patients had measurable disease at baseline in the palbociclib plus letrozole and placebo plus letrozole arms, respectively.
Arm/Group Title Palbociclib Plus Letrozole Placebo Plus Letrozole
Hide Arm/Group Description:
Participants received letrozole 2.5 milligram (mg) orally QD (once daily) combined with palbociclib 125 mg QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Participants received letrozole 2.5 mg orally QD combined with placebo QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Overall Number of Participants Analyzed 338 171
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
60.7
(55.2 to 65.9)
49.1
(41.4 to 56.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments Stratified analysis: Stratified by disease site (visceral vs non-visceral) per randomization.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0090
Comments 1-sided p-value is from exact test.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.594
Confidence Interval (2-Sided) 95%
1.080 to 2.347
Estimation Comments An Odds Ratio >1 means better response in favor of the palbociclib plus letrozole arm.
4.Secondary Outcome
Title Duration of Response (DR)
Hide Description DR is 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 occurs first. If tumor progression data included more than 1 date, the first date will be used. DR was calculated as [the date response ended (i.e. date of PD or death) - first CR or PR date + 1)]/30.4. DR would only be calculated for the subgroup of patients with an objective tumor response. Per RECIST v1.1, CR: Complete disappearance of target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis <10mm). PR: ≥30% decrease under baseline of the sum of diameters of all target measurable lesions.The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. Stable Disease: neither sufficient shrinkage nor increase to qualify for disease progression.
Time Frame From randomization until end of treatment (up to approximately 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who had tumor response with CR or PR during study. A total of 206 and 85 patients had objective response in the palbociclib plus letrozole and placebo plus letrozole arms, respectively.
Arm/Group Title Palbociclib Plus Letrozole Placebo Plus Letrozole
Hide Arm/Group Description:
Participants received letrozole 2.5 milligram (mg) orally QD (once daily) combined with palbociclib 125 mg QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Participants received letrozole 2.5 mg orally QD combined with placebo QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Overall Number of Participants Analyzed 206 85
Median (95% Confidence Interval)
Unit of Measure: Months
20.1
(19.3 to 28.0)
16.7
(13.8 to 22.5)
5.Secondary Outcome
Title Disease Control (DC)/Clinical Benefit Response (CBR)
Hide Description DC is defined as the overall CR, PR, or stable disease (SD) ≥24 weeks according to the RECIST version 1.1. Disease Control Rate (DCR) is defined as the patients with CR, PR, or SD ≥24 weeks relative to all randomized participants. Participants who do not have on-study radiographic tumor reevaluation, who received anti-tumor treatment, a best response of SD≥24 weeks, or who died, progressed,or dropped out for any reason prior to achieving reaching a CR or PR and a best response of SD≥24 weeks was counted as non-responders in DCR. Per RECIST v1.1, CR: Complete disappearance of target lesions with exception of nodal disease. All target nodes must decrease to normal size (short axis <10mm). PR: ≥30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter is used in the sum for target nodes, while the longest diameter is used in the sum for all other target lesions. SD: neither sufficient shrinkage nor increase to qualify for disease progression
Time Frame From randomization until end of treatment (up to approximately 2.5 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population or full analysis set included all participants who were randomized, with study medication, regardless of whether participants received study medication or received a different drug from that to which they were randomized.
Arm/Group Title Palbociclib Plus Letrozole Placebo Plus Letrozole
Hide Arm/Group Description:
Participants received letrozole 2.5 milligram (mg) orally QD (once daily) combined with palbociclib 125 mg QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Participants received letrozole 2.5 mg orally QD combined with placebo QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Overall Number of Participants Analyzed 444 222
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
85.8
(82.2 to 88.9)
71.2
(64.7 to 77.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments Stratified analysis: Stratified by disease site (visceral, non-visceral) per randomization.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 1-sided p-value is from exact test.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.451
Confidence Interval (2-Sided) 95%
1.619 to 3.722
Estimation Comments An Odds Ratio > 1 means better response in favor of palbociclib plus letrozole arm.
6.Secondary Outcome
Title Tumor Tissue Biomarkers, Including Genes (eg, Copy Numbers of CCND1, CDKN2A), Proteins (eg, Ki67, pRb), and RNA Expression (eg, cdk4, cdk6): Protein Biomarker Analyses by Using Immunohistochemistry Are Presented
Hide Description

PFS survival by biomarker status by Investigator assessment. Progression is 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.

Positive is defined as H-Score ≥1 and negative as H-Score <1. H-Score is calculated as the sum of the % of cells at each level of staining intensity (0, 1+, 2+, and 3+) multiplied by the staining intensity value: H-Score = (% at 0)*0 + (% at 1+)*1 + (% at 2+)*2 + (% at 3+)*3. H-Score values range from 0 to 300.

ER stands for estrogen receptor and Rb stands for retinoblastoma susceptibility gene product.

Time Frame From randomization until end of treatment (up to approximately 24 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population or full analysis set included all participants who were randomized, with study medication, regardless of whether participants received study medication or received a different drug from that to which they were randomized.
Arm/Group Title Palbociclib Plus Letrozole Placebo Plus Letrozole
Hide Arm/Group Description:
Participants received letrozole 2.5 milligram (mg) orally QD (once daily) combined with palbociclib 125 mg QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Participants received letrozole 2.5 mg orally QD combined with placebo QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Overall Number of Participants Analyzed 444 222
Median (95% Confidence Interval)
Unit of Measure: Months
ER Positive (N= 338, 166)
24.9 [1] 
(22.2 to NA)
16.3
(12.9 to 19.1)
ER Negative (N= 40, 22)
15.6
(8.3 to 22.0)
5.4
(2.7 to 11.1)
Rb Positive (N= 345, 167)
24.2
(21.4 to 25.7)
13.7
(11.0 to 16.5)
Rb Negative (N= 29, 22)
NA [1] 
(11.4 to NA)
18.5 [1] 
(2.9 to NA)
Cyclin D1 Positive (N= 370, 179)
24.8
(21.5 to 27.6)
13.8
(11.3 to 16.8)
Cyclin D1 Negative (N= 5, 10)
11.1
(2.2 to 23.9)
8.1 [1] 
(0.4 to NA)
p16 Positive (N= 305, 161)
24.8 [1] 
(21.5 to NA)
13.8
(11.1 to 16.8)
p16 Negative (N= 59, 25)
16.8
(11.1 to 24.9)
13.8 [1] 
(8.1 to NA)
p16 H-Score<175 (N= 341, 177)
23.7
(19.6 to 25.7)
13.8
(11.2 to 16.8)
p16 H-Score≥175 (N= 23, 9)
24.2 [1] 
(11.1 to NA)
5.6
(1.5 to 19.1)
Ki67 ≤20% (N= 216, 102)
27.6 [1] 
(24.2 to NA)
16.8
(13.7 to 22.0)
Ki67 >20% (N= 152, 83)
17.5
(13.8 to 22.0)
8.4
(5.6 to 13.6)
[1]
Not reached; insufficient number of participants with events.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments Statistical analysis for ER positive
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Unstratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.571
Confidence Interval (2-Sided) 95%
0.443 to 0.737
Estimation Comments Unstratified Cox proportional hazards model was used.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments Statistical analysis for ER Negative
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0030
Comments [Not Specified]
Method Unstratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.405
Confidence Interval (2-Sided) 95%
0.218 to 0.751
Estimation Comments Unstratified Cox proportional hazards model was used.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments Statistical analysis for Rb Positive
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Unstratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.531
Confidence Interval (2-Sided) 95%
0.416 to 0.680
Estimation Comments Unstratified Cox proportional hazards model was used.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments Statistical analysis for Rb Negative
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3237
Comments [Not Specified]
Method Unstratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.675
Confidence Interval (2-Sided) 95%
0.308 to 1.481
Estimation Comments Unstratified Cox proportional hazards model was used.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments Statistical analysis for Cyclin D1 Positive
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Unstratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.555
Confidence Interval (2-Sided) 95%
0.437 to 0.705
Estimation Comments Unstratified Cox proportional hazards model was used.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments Statistical analysis for Cyclin D1 Negative
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9964
Comments [Not Specified]
Method Unstratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.997
Confidence Interval (2-Sided) 95%
0.287 to 3.461
Estimation Comments Unstratified Cox proportional hazards model was used.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments Statistical analysis for p16 Positive
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Unstratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.518
Confidence Interval (2-Sided) 95%
0.400 to 0.670
Estimation Comments Unstratified Cox proportional hazards model was used.
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments Statistical analysis for p16 Negative
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3221
Comments [Not Specified]
Method Unstratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.731
Confidence Interval (2-Sided) 95%
0.392 to 1.364
Estimation Comments Unstratified Cox proportional hazards model was used.
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments Statistical analysis for p16 HScore<175
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Unstratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.581
Confidence Interval (2-Sided) 95%
0.455 to 0.742
Estimation Comments Unstratified Cox proportional hazards model was used.
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments Statistical analysis for p16 HScore≥175
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0022
Comments [Not Specified]
Method Unstratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.255
Confidence Interval (2-Sided) 95%
0.100 to 0.650
Estimation Comments Unstratified Cox proportional hazards model was used.
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments Statistical analysis for Ki67 ≤20%
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Unstratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.530
Confidence Interval (2-Sided) 95%
0.379 to 0.742
Estimation Comments Unstratified Cox proportional hazards model was used.
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments Statistical analysis for Ki67 >20%
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments [Not Specified]
Method Unstratified log-rank test
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.569
Confidence Interval (2-Sided) 95%
0.409 to 0.791
Estimation Comments Unstratified Cox proportional hazards model was used.
7.Secondary Outcome
Title Corrected QT Interval (QTc) Time-matched Change From Baseline on Cycle 1 Day 14
Hide Description Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and sent to a central laboratory for blinded manual adjudication. The average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR), by Bazette's formula (QTcB = QT divided by square root of RR) and corrected QT interval according to study-specific criteria (QTcS). Time-matched change from baseline values were reported for QTc analysis population.
Time Frame Time-matched triplicate ECGs were collected at 0 (predose), 2, 4, 6 and 8 hours on Day 0 and on Cycle1 Day14
Hide Outcome Measure Data
Hide Analysis Population Description
QTc analysis set is a subset of as treated (AT) population who were in Group 1; their QTc was used to study the effect of palbociclib on QT interval via serial triplicate ECGs with PK draws; and who had ≥ 1 pair of time-matched Day 0 and palbociclib postdose (Cycle1 Day14) measurements.
Arm/Group Title Palbociclib Plus Letrozole Placebo Plus Letrozole
Hide Arm/Group Description:
Participants received letrozole 2.5 milligram (mg) orally QD (once daily) combined with palbociclib 125 mg QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Participants received letrozole 2.5 mg orally QD combined with placebo QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Overall Number of Participants Analyzed 76 47
Least Squares Mean (90% Confidence Interval)
Unit of Measure: msec
QTcS at 0 hour
0.80
(-1.67 to 3.26)
2.95
(-0.19 to 6.10)
QTcS at 2 hour
3.32
(0.79 to 5.85)
1.65
(-1.48 to 4.78)
QTcS at 4 hour
2.76
(0.23 to 5.30)
1.74
(-1.39 to 4.87)
QTcS at 6 hour
4.49
(1.96 to 7.02)
0.72
(-2.41 to 3.85)
QTcS at 8 hour
0.94
(-1.60 to 3.48)
3.14
(0.01 to 6.27)
QTcF at 0 hour
1.10
(-1.39 to 3.58)
3.06
(-0.11 to 6.23)
QTcF at 2 hour
3.68
(1.12 to 6.23)
1.73
(-1.43 to 4.88)
QTcF at 4 hour
2.86
(0.31 to 5.41)
1.54
(-1.62 to 4.70)
QTcF at 6 hour
4.57
(2.01 to 7.12)
0.71
(-2.44 to 3.87)
QTcF at 8 hour
1.21
(-1.36 to 3.77)
2.84
(-0.31 to 6.00)
QTcB at 0 hour
-0.11
(-2.83 to 2.61)
2.78
(-0.69 to 6.25)
QTcB at 2 hour
1.46
(-1.34 to 4.25)
0.83
(-2.63 to 4.28)
QTcB at 4 hour
2.58
(-0.22 to 5.38)
2.47
(-0.98 to 5.92)
QTcB at 6 hour
4.03
(1.24 to 6.83)
0.53
(-2.92 to 3.99)
QTcB at 8 hour
-0.17
(-2.98 to 2.64)
4.14
(0.69 to 7.59)
8.Secondary Outcome
Title Corrected QT Interval (QTc)
Hide Description Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and sent to a central laboratory for blinded manual adjudication. The average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR), by Bazette's formula (QTcB = QT divided by square root of RR) and corrected QT interval according to study-specific criteria (QTcS). Percentage of participants with post-baseline maximum absolute values and maximum increase from baseline were summarized for the safety analysis population.
Time Frame For safety monitoring triplicate ECGs were obtained at 0 hour (pre-dose) on Day 1 of Cycle 1, Day 14 of Cycles 1 and Cycle 2, then on Day 1 of Cycles 4, 7, and 10. ECGs beyond Cycle 10 were performed as clinically indicated
Hide Outcome Measure Data
Hide Analysis Population Description
The AT population or safety analysis set 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 Plus Letrozole Placebo Plus Letrozole
Hide Arm/Group Description:
Participants received letrozole 2.5 milligram (mg) orally QD (once daily) combined with palbociclib 125 mg QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Participants received letrozole 2.5 mg orally QD combined with placebo QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Overall Number of Participants Analyzed 441 220
Measure Type: Number
Unit of Measure: Percentage of participants
Maximum QTcS <450 msec 80.5 85.9
Maximum QTcS 450-<480 msec 17.9 11.8
Maximum QTcS 480-<500 msec 1.1 2.3
Maximum QTcS ≥500 msec 0.5 0
Maximum QTcF <450 msec 85.9 89.5
Maximum QTcF 450-<480 msec 12.2 9.5
Maximum QTcF 480-<500 msec 1.6 0.9
Maximum QTcF ≥500 msec 0.2 0
Maximum QTcB <450 msec 64.9 69.1
Maximum QTcB 450-<480 msec 32.2 27.3
Maximum QTcB 480-<500 msec 2.3 3.2
Maximum QTcB ≥500 msec 0.7 0.5
Maximum QTcS Change <30 msec 92.7 94.5
Maximum QTcS 30≤Change <60 msec 6.6 5.5
Maximum QTcS Change≥60 msec 0.7 0
Maximum QTcF Change <30 msec 91.6 93.6
Maximum QTcF 30≤Change <60 msec 7.9 6.4
Maximum QTcF Change≥60 msec 0.5 0
Maximum QTcB Change <30 msec 88.9 91.4
Maximum QTcB 30≤Change <60 msec 10.2 8.2
Maximum QTcB Change≥60 msec 0.9 0.5
9.Secondary Outcome
Title Observed Plasma Trough Concentration (Ctrough) at Steady-State
Hide Description Summary of Plasma Palbociclib Within-Patient Mean Steady-State Trough Concentrations.
Time Frame 0 hour (predose) on Day 14 of cycles 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis set was a subset of AT participants, who were treated with Palbociclib and had at least one measured plasma concentration.
Arm/Group Title Palbociclib Plus Letrozole
Hide Arm/Group Description:
Participants received letrozole 2.5 milligram (mg) orally QD (once daily) combined with palbociclib 125 mg QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Overall Number of Participants Analyzed 423
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cycle 1 Day 14 (N= 395)
70.1
(59%)
Cycle 2 Day 14 (N= 401)
64.2
(82%)
10.Secondary Outcome
Title Change From Baseline Between Treatment Comparison in Euro Quality of Life (EQ-5D) Index
Hide Description The EuroQol EQ-5D is a 6-item instrument designed to assess health status in terms of a single index value or utility score. It contains 5 descriptors of current health state (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) with each dimension having 3 levels of function (1=no problem, 2=some problem, and 3=extreme problem). The scores on the 5 descriptors are summarized to create a single summary score. An overall utility score is calculated based on these domains, with a range score from 0 (worse health scenario) to a maximum of 1.0 (best health scenario).
Time Frame From Baseline up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Patient Reported Outcome (PRO) Analysis Set is a subset of ITT participants, who had both baseline and at least one follow-up PRO assessment.
Arm/Group Title Palbociclib Plus Letrozole Placebo Plus Letrozole
Hide Arm/Group Description:
Participants received letrozole 2.5 milligram (mg) orally QD (once daily) combined with palbociclib 125 mg QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Participants received letrozole 2.5 mg orally QD combined with placebo QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Overall Number of Participants Analyzed 437 218
Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
0.014
(0.00 to 0.03)
-0.010
(-0.03 to 0.01)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0925
Comments [Not Specified]
Method Mixed Models Analysis
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.023
Confidence Interval (2-Sided) 95%
-0.004 to 0.051
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline Between Treatment Comparison in Functional Assessment of Cancer Therapy -Breast (FACT-B)
Hide Description FACT is a modular approach to assess participant health-related quality of life using a 'core' set of questions (FACT-G) as well as a cancer site-specific module. The FACT-G is a 27-item compilation of general questions divided into 4 domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. The FACT-B consisted of the FACT-G (27-item) and a breast-specific module: a 10-item instrument designed to assess participant concerns relating to breast cancer. For all questions, participants were asked to respond to a five-level scale where 0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, and 4=very much. FACT-B total score = Physical Well-Being + Social/Family Well-Being + Emotional Well-Being + Functional Well-Being + Breast Cancer Subscale. As each of the items ranges from 0-4, the range of possible scores is 0-144, with 0 being the worst possible score and 144 the best.
Time Frame From Baseline up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Patient Reported Outcome (PRO) Analysis Set is a subset of ITT participants, who had both baseline and at least one follow-up PRO assessment.
Arm/Group Title Palbociclib Plus Letrozole Placebo Plus Letrozole
Hide Arm/Group Description:
Participants received letrozole 2.5 milligram (mg) orally QD (once daily) combined with palbociclib 125 mg QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Participants received letrozole 2.5 mg orally QD combined with placebo QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Overall Number of Participants Analyzed 439 218
Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
-0.106
(-1.42 to 1.21)
0.219
(-1.68 to 2.12)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palbociclib Plus Letrozole, Placebo Plus Letrozole
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7822
Comments [Not Specified]
Method Mixed Models Analysis
Comments Analysis based on repeated measures mixed-effects model with an intercept term, treatment, time, treatment-by-time, and baseline as covariate.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.325
Confidence Interval (2-Sided) 95%
-2.63 to 1.98
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities)
Hide Description An AE is any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE is any untoward medical occurrence at any dose that results in death; is life-threatening; requires hospitalization; results in persistent or significant disability or in congenital anomaly/birth defect. Severity will be graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.
Time Frame From the participant randomization up to 28 days after last dose of study drug, up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
AT population = ITT population because all the participants randomized were treated with study drugs per study design.
Arm/Group Title Palbociclib Plus Letrozole Placebo Plus Letrozole
Hide Arm/Group Description:
Participants received letrozole 2.5 milligram (mg) orally QD (once daily) combined with palbociclib 125 mg QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Participants received letrozole 2.5 mg orally QD combined with placebo QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
Overall Number of Participants Analyzed 444 222
Measure Type: Number
Unit of Measure: Percentage of Participants
Participants with AEs 98.9 95.5
Participants with SAEs 19.6 12.6
Participants with Grade 3 or 4 AEs 77.5 25.2
Participants with Grade 5 AEs 2.3 1.8
Permanently discontinued study due to AEs 2.5 1.8
Permanently disc. palbociclib/placebo due to AEs 9.2 5.4
Permanently discontinued letrozole due to AEs 6.1 5.0
Temporarily disc. palbociclib/placebo due to AEs 74.8 15.8
Temporarily discontinued letrozole due to AEs 17.3 9.9
With palbociclib/placebo dose reduction due to AEs 36.0 1.4
Time Frame From the date of randomization up to 28 days after last dose of study medication, up to 2.5 years.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Palbociclib Plus Letrozole Placebo Plus Letrozole
Hide Arm/Group Description Participants received letrozole 2.5 milligram (mg) orally QD (once daily) combined with palbociclib 125 mg QD for 21 days of every-28-day cycle, followed by 7 days off treatment. Participants received letrozole 2.5 mg orally QD combined with placebo QD for 21 days of every-28-day cycle, followed by 7 days off treatment.
All-Cause Mortality
Palbociclib Plus Letrozole Placebo Plus Letrozole
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Palbociclib Plus Letrozole Placebo Plus Letrozole
Affected / at Risk (%) Affected / at Risk (%)
Total   87/444 (19.59%)   28/222 (12.61%) 
Blood and lymphatic system disorders     
Anaemia * 1  2/444 (0.45%)  0/222 (0.00%) 
Febrile neutropenia * 1  7/444 (1.58%)  0/222 (0.00%) 
Cardiac disorders     
Acute myocardial infarction * 1  1/444 (0.23%)  0/222 (0.00%) 
Aortic valve stenosis * 1  1/444 (0.23%)  0/222 (0.00%) 
Atrial fibrillation * 1  2/444 (0.45%)  0/222 (0.00%) 
Atrioventricular block * 1  1/444 (0.23%)  0/222 (0.00%) 
Cardiac arrest * 1  0/444 (0.00%)  1/222 (0.45%) 
Cardiogenic shock * 1  1/444 (0.23%)  0/222 (0.00%) 
Cardiopulmonary failure * 1  1/444 (0.23%)  0/222 (0.00%) 
Cardiovascular insufficiency * 1  1/444 (0.23%)  0/222 (0.00%) 
Myocardial infarction * 1  1/444 (0.23%)  0/222 (0.00%) 
Pericardial effusion * 1  1/444 (0.23%)  0/222 (0.00%) 
Endocrine disorders     
Hypercalcaemia of malignancy * 1  0/444 (0.00%)  1/222 (0.45%) 
Hyperthyroidism * 1  0/444 (0.00%)  1/222 (0.45%) 
Eye disorders     
Cataract * 1  1/444 (0.23%)  0/222 (0.00%) 
Gastrointestinal disorders     
Abdominal pain upper * 1  1/444 (0.23%)  0/222 (0.00%) 
Colitis * 1  0/444 (0.00%)  1/222 (0.45%) 
Constipation * 1  1/444 (0.23%)  0/222 (0.00%) 
Diarrhoea * 1  1/444 (0.23%)  0/222 (0.00%) 
Gastrooesophageal reflux disease * 1  1/444 (0.23%)  0/222 (0.00%) 
Haemorrhoids * 1  1/444 (0.23%)  0/222 (0.00%) 
Intestinal obstruction * 1  1/444 (0.23%)  0/222 (0.00%) 
Large intestinal obstruction * 1  1/444 (0.23%)  0/222 (0.00%) 
Mechanical ileus * 1  1/444 (0.23%)  0/222 (0.00%) 
Nausea * 1  0/444 (0.00%)  1/222 (0.45%) 
Pancreatitis * 1  1/444 (0.23%)  0/222 (0.00%) 
Pancreatitis acute * 1  2/444 (0.45%)  0/222 (0.00%) 
Small intestinal obstruction * 1  1/444 (0.23%)  0/222 (0.00%) 
Vomiting * 1  2/444 (0.45%)  2/222 (0.90%) 
General disorders     
Chest pain * 1  1/444 (0.23%)  1/222 (0.45%) 
Death * 1  1/444 (0.23%)  0/222 (0.00%) 
Device dislocation * 1  0/444 (0.00%)  1/222 (0.45%) 
Disease progression * 1  3/444 (0.68%)  0/222 (0.00%) 
General physical health deterioration * 1  1/444 (0.23%)  1/222 (0.45%) 
Non-cardiac chest pain * 1  1/444 (0.23%)  0/222 (0.00%) 
Pain * 1  2/444 (0.45%)  1/222 (0.45%) 
Puncture site pain * 1  1/444 (0.23%)  0/222 (0.00%) 
Pyrexia * 1  3/444 (0.68%)  0/222 (0.00%) 
Hepatobiliary disorders     
Bile duct stenosis * 1  1/444 (0.23%)  0/222 (0.00%) 
Biliary colic * 1  1/444 (0.23%)  0/222 (0.00%) 
Infections and infestations     
Appendicitis * 1  1/444 (0.23%)  0/222 (0.00%) 
Breast cellulitis * 1  1/444 (0.23%)  0/222 (0.00%) 
Bronchiolitis * 1  1/444 (0.23%)  0/222 (0.00%) 
Bronchitis * 1  1/444 (0.23%)  0/222 (0.00%) 
Cellulitis * 1  2/444 (0.45%)  0/222 (0.00%) 
Clostridium difficile infection * 1  1/444 (0.23%)  0/222 (0.00%) 
Cystitis * 1  1/444 (0.23%)  0/222 (0.00%) 
Diverticulitis * 1  0/444 (0.00%)  2/222 (0.90%) 
Erysipelas * 1  1/444 (0.23%)  0/222 (0.00%) 
Influenza * 1  1/444 (0.23%)  0/222 (0.00%) 
Lower respiratory tract infection * 1  0/444 (0.00%)  1/222 (0.45%) 
Lower respiratory tract infection bacterial * 1  0/444 (0.00%)  1/222 (0.45%) 
Peritonitis bacterial * 1  0/444 (0.00%)  1/222 (0.45%) 
Pharyngitis streptococcal * 1  1/444 (0.23%)  0/222 (0.00%) 
Pneumonia * 1  4/444 (0.90%)  2/222 (0.90%) 
Pyelonephritis * 1  1/444 (0.23%)  0/222 (0.00%) 
Respiratory tract infection * 1  0/444 (0.00%)  1/222 (0.45%) 
Sepsis * 1  2/444 (0.45%)  0/222 (0.00%) 
Staphylococcal bacteraemia * 1  1/444 (0.23%)  0/222 (0.00%) 
Tracheobronchitis * 1  1/444 (0.23%)  0/222 (0.00%) 
Urinary tract infection * 1  3/444 (0.68%)  0/222 (0.00%) 
Urosepsis * 1  1/444 (0.23%)  0/222 (0.00%) 
Injury, poisoning and procedural complications     
Ankle fracture * 1  1/444 (0.23%)  0/222 (0.00%) 
Fall * 1  1/444 (0.23%)  0/222 (0.00%) 
Femoral neck fracture * 1  0/444 (0.00%)  1/222 (0.45%) 
Femur fracture * 1  1/444 (0.23%)  0/222 (0.00%) 
Foot fracture * 1  1/444 (0.23%)  0/222 (0.00%) 
Fracture displacement * 1  1/444 (0.23%)  0/222 (0.00%) 
Gastroenteritis radiation * 1  1/444 (0.23%)  0/222 (0.00%) 
Lower limb fracture * 1  1/444 (0.23%)  0/222 (0.00%) 
Meniscus injury * 1  1/444 (0.23%)  0/222 (0.00%) 
Pelvic fracture * 1  1/444 (0.23%)  0/222 (0.00%) 
Spinal fracture * 1  0/444 (0.00%)  1/222 (0.45%) 
Wound secretion * 1  1/444 (0.23%)  0/222 (0.00%) 
Investigations     
Alanine aminotransferase increased * 1  2/444 (0.45%)  0/222 (0.00%) 
Aspartate aminotransferase increased * 1  2/444 (0.45%)  0/222 (0.00%) 
Neutrophil count decreased * 1  1/444 (0.23%)  0/222 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  1/444 (0.23%)  0/222 (0.00%) 
Hyperglycaemia * 1  0/444 (0.00%)  1/222 (0.45%) 
Musculoskeletal and connective tissue disorders     
Bone pain * 1  1/444 (0.23%)  0/222 (0.00%) 
Pain in jaw * 1  0/444 (0.00%)  1/222 (0.45%) 
Pathological fracture * 1  2/444 (0.45%)  0/222 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute leukaemia * 1  0/444 (0.00%)  1/222 (0.45%) 
Basal cell carcinoma * 1  1/444 (0.23%)  0/222 (0.00%) 
Cervix carcinoma * 1  0/444 (0.00%)  1/222 (0.45%) 
Endometrial cancer * 1  0/444 (0.00%)  1/222 (0.45%) 
Malignant melanoma * 1  3/444 (0.68%)  0/222 (0.00%) 
Ovarian germ cell teratoma benign * 1  1/444 (0.23%)  0/222 (0.00%) 
Papillary thyroid cancer * 1  0/444 (0.00%)  1/222 (0.45%) 
Nervous system disorders     
Cauda equina syndrome * 1  0/444 (0.00%)  1/222 (0.45%) 
Cerebral haemorrhage * 1  1/444 (0.23%)  0/222 (0.00%) 
Cerebrovascular accident * 1  1/444 (0.23%)  0/222 (0.00%) 
Headache * 1  1/444 (0.23%)  1/222 (0.45%) 
Hemiparesis * 1  1/444 (0.23%)  0/222 (0.00%) 
Paraesthesia * 1  0/444 (0.00%)  1/222 (0.45%) 
Seizure * 1  1/444 (0.23%)  0/222 (0.00%) 
Syncope * 1  2/444 (0.45%)  0/222 (0.00%) 
Thrombotic cerebral infarction * 1  1/444 (0.23%)  0/222 (0.00%) 
Psychiatric disorders     
Depression * 1  0/444 (0.00%)  1/222 (0.45%) 
Renal and urinary disorders     
Acute kidney injury * 1  3/444 (0.68%)  0/222 (0.00%) 
Hydronephrosis * 1  1/444 (0.23%)  0/222 (0.00%) 
Renal tubular necrosis * 1  0/444 (0.00%)  1/222 (0.45%) 
Stag horn calculus * 1  1/444 (0.23%)  1/222 (0.45%) 
Urinary tract obstruction * 1  1/444 (0.23%)  0/222 (0.00%) 
Reproductive system and breast disorders     
Breast haematoma * 1  1/444 (0.23%)  0/222 (0.00%) 
Uterovaginal prolapse * 1  1/444 (0.23%)  0/222 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease * 1  1/444 (0.23%)  0/222 (0.00%) 
Dyspnoea * 1  1/444 (0.23%)  0/222 (0.00%) 
Interstitial lung disease * 1  1/444 (0.23%)  0/222 (0.00%) 
Pleural effusion * 1  4/444 (0.90%)  1/222 (0.45%) 
Pneumonitis * 1  1/444 (0.23%)  0/222 (0.00%) 
Pulmonary embolism * 1  4/444 (0.90%)  3/222 (1.35%) 
Respiratory failure * 1  1/444 (0.23%)  0/222 (0.00%) 
Tracheomalacia * 1  0/444 (0.00%)  1/222 (0.45%) 
Skin and subcutaneous tissue disorders     
Dermatitis * 1  1/444 (0.23%)  0/222 (0.00%) 
Rash maculo-papular * 1  1/444 (0.23%)  0/222 (0.00%) 
Vascular disorders     
Deep vein thrombosis * 1  2/444 (0.45%)  1/222 (0.45%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (v18.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Palbociclib Plus Letrozole Placebo Plus Letrozole
Affected / at Risk (%) Affected / at Risk (%)
Total   433/444 (97.52%)   206/222 (92.79%) 
Blood and lymphatic system disorders     
Anaemia * 1  103/444 (23.20%)  20/222 (9.01%) 
Leukopenia * 1  106/444 (23.87%)  1/222 (0.45%) 
Neutropenia * 1  294/444 (66.22%)  7/222 (3.15%) 
Thrombocytopenia * 1  44/444 (9.91%)  2/222 (0.90%) 
Eye disorders     
Lacrimation increased * 1  25/444 (5.63%)  2/222 (0.90%) 
Gastrointestinal disorders     
Abdominal distension * 1  18/444 (4.05%)  12/222 (5.41%) 
Abdominal pain * 1  50/444 (11.26%)  12/222 (5.41%) 
Abdominal pain upper * 1  26/444 (5.86%)  17/222 (7.66%) 
Constipation * 1  86/444 (19.37%)  34/222 (15.32%) 
Diarrhoea * 1  116/444 (26.13%)  43/222 (19.37%) 
Dry mouth * 1  25/444 (5.63%)  11/222 (4.95%) 
Dyspepsia * 1  41/444 (9.23%)  27/222 (12.16%) 
Gastrooesophageal reflux disease * 1  27/444 (6.08%)  7/222 (3.15%) 
Nausea * 1  156/444 (35.14%)  57/222 (25.68%) 
Stomatitis * 1  68/444 (15.32%)  13/222 (5.86%) 
Vomiting * 1  69/444 (15.54%)  35/222 (15.77%) 
General disorders     
Asthenia * 1  75/444 (16.89%)  26/222 (11.71%) 
Fatigue * 1  166/444 (37.39%)  61/222 (27.48%) 
Influenza like illness * 1  25/444 (5.63%)  10/222 (4.50%) 
Mucosal inflammation * 1  41/444 (9.23%)  8/222 (3.60%) 
Oedema peripheral * 1  50/444 (11.26%)  14/222 (6.31%) 
Pain * 1  34/444 (7.66%)  20/222 (9.01%) 
Pyrexia * 1  53/444 (11.94%)  19/222 (8.56%) 
Infections and infestations     
Nasopharyngitis * 1  62/444 (13.96%)  22/222 (9.91%) 
Oral herpes * 1  28/444 (6.31%)  3/222 (1.35%) 
Sinusitis * 1  23/444 (5.18%)  7/222 (3.15%) 
Upper respiratory tract infection * 1  59/444 (13.29%)  25/222 (11.26%) 
Urinary tract infection * 1  52/444 (11.71%)  17/222 (7.66%) 
Injury, poisoning and procedural complications     
Fall * 1  35/444 (7.88%)  11/222 (4.95%) 
Investigations     
Alanine aminotransferase increased * 1  43/444 (9.68%)  9/222 (4.05%) 
Aspartate aminotransferase increased * 1  42/444 (9.46%)  11/222 (4.95%) 
Neutrophil count decreased * 1  87/444 (19.59%)  7/222 (3.15%) 
Platelet count decreased * 1  27/444 (6.08%)  1/222 (0.45%) 
Weight decreased * 1  23/444 (5.18%)  10/222 (4.50%) 
White blood cell count decreased * 1  72/444 (16.22%)  4/222 (1.80%) 
Metabolism and nutrition disorders     
Decreased appetite * 1  65/444 (14.64%)  20/222 (9.01%) 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1  148/444 (33.33%)  75/222 (33.78%) 
Back pain * 1  96/444 (21.62%)  48/222 (21.62%) 
Bone pain * 1  38/444 (8.56%)  22/222 (9.91%) 
Muscle spasms * 1  37/444 (8.33%)  12/222 (5.41%) 
Musculoskeletal chest pain * 1  25/444 (5.63%)  9/222 (4.05%) 
Musculoskeletal pain * 1  37/444 (8.33%)  16/222 (7.21%) 
Myalgia * 1  53/444 (11.94%)  20/222 (9.01%) 
Neck pain * 1  23/444 (5.18%)  10/222 (4.50%) 
Pain in extremity * 1  68/444 (15.32%)  39/222 (17.57%) 
Nervous system disorders     
Dizziness * 1  63/444 (14.19%)  33/222 (14.86%) 
Dysgeusia * 1  45/444 (10.14%)  11/222 (4.95%) 
Headache * 1  95/444 (21.40%)  58/222 (26.13%) 
Psychiatric disorders     
Anxiety * 1  36/444 (8.11%)  25/222 (11.26%) 
Depression * 1  34/444 (7.66%)  20/222 (9.01%) 
Insomnia * 1  66/444 (14.86%)  26/222 (11.71%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  111/444 (25.00%)  42/222 (18.92%) 
Dyspnoea * 1  66/444 (14.86%)  30/222 (13.51%) 
Epistaxis * 1  41/444 (9.23%)  14/222 (6.31%) 
Oropharyngeal pain * 1  41/444 (9.23%)  7/222 (3.15%) 
Skin and subcutaneous tissue disorders     
Alopecia * 1  146/444 (32.88%)  35/222 (15.77%) 
Dry skin * 1  55/444 (12.39%)  13/222 (5.86%) 
Pruritus * 1  39/444 (8.78%)  8/222 (3.60%) 
Rash * 1  61/444 (13.74%)  22/222 (9.91%) 
Vascular disorders     
Hot flush * 1  93/444 (20.95%)  68/222 (30.63%) 
Hypertension * 1  28/444 (6.31%)  21/222 (9.46%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (v18.1)
For Overall Survival: The patients continue to be followed for survival and the final OS analysis will be performed when 390 deaths have been reported. OS should not be reported at this time because the OS data is still being followed.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01740427    
Other Study ID Numbers: A5481008
2012-004601-27 ( EudraCT Number )
PALMOA-2 ( Other Identifier: Alias Study Number )
PALOMA-2 ( Other Identifier: Alias Study Number )
First Submitted: November 26, 2012
First Posted: December 4, 2012
Results First Submitted: October 21, 2016
Results First Posted: April 26, 2017
Last Update Posted: February 24, 2020