Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Recurrence

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Letrozole

Estrogens

Palbociclib

Aromatase Inhibitors

Enzyme Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Protein Kinase Inhibitors

PD-0332991, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously).

Placebo, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously).

PD-0332991, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment

PD-0332991

Letrozole, 2.5mg, orally once daily (continuously)

Placebo, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment

Placebo

Pfizer CT.gov Call Center

The study is designed to compare the clinical benefit following treatment with letrozole in combination with PD-0332991 versus letrozole in combination with placebo in postmenopausal women with ER(+)/HER2(-) advanced breast cancer who have not received prior systemic anti cancer therapies for their advanced/metastatic disease.

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

A RANDOMIZED, MULTICENTER, DOUBLE-BLIND PHASE 3 STUDY OF PD-0332991 (ORAL CDK 4/6 INHIBITOR) PLUS LETROZOLE VERSUS PLACEBO PLUS LETROZOLE FOR THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH ER (+), HER2 (-) BREAST CANCER WHO HAVE NOT RECEIVED ANY PRIOR SYSTEMIC ANTI CANCER TREATMENT FOR ADVANCED DISEASE

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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.

Objective Response (OR) 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.

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.

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.

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

PFS 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.

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.

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.

Summary of Plasma Palbociclib Within-Patient Mean Steady-State Trough Concentrations.

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).

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.

An AE was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. SAE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization; resulted in persistent or significant disability or in congenital anomaly/birth defect. TEAE were events that occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Severity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0 as Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening and Grade 5 = death related to AE.

OS was defined as the time from date of randomization to date of death due to any cause. Participants without survival data beyond the date of their last follow-up were censored on the last date they were known to be alive.

One, two or three-year survival probability was defined as the probability of survival 1 year, 2 or 3 years after the date of randomization. The survival probability was estimated using the Kaplan-Meier method and 2-sided 95% confidence interval (CI) was calculated using the product limit method.

Laboratory abnormalities included anemia, hemoglobin increased, neutrophils (absolute), platelets, white blood cells, alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), bilirubin (total), creatinine, hypercalcemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypokalemia, hypomagnesemia and hyponatremia. Laboratory abnormalities were graded by CTCAE version (v) 4.0 as Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe and Grade 4 = life-threatening. Categories with at least 1 non-zero data values are reported.

Pfizer

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.

Palbociclib Plus Letrozole

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.

Placebo Plus Letrozole

Total

Age, Continuous

Sex: Female, Male

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.

Pfizer ClinicalTrials.gov Call Center

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.

Progression-Free Survival (PFS) as Assessed by the Investigator.

Stratified analysis: Stratified by disease site (visceral vs non-visceral) per randomization.

Objective Response as Assessed by the Investigator

Patients who had measurable disease at baseline.

Objective Response: Patients With Measurable Disease at Baseline as Assessed by the Investigator

Patients who had tumor response with CR or PR during study.

Duration of Response (DR)

Stratified analysis: Stratified by disease site (visceral, non-visceral) per randomization.

Disease Control (DC)/Clinical Benefit Response (CBR)

Statistical analysis for Cyclin D1 Positive

Statistical analysis for Cyclin D1 Negative

Statistical analysis for p16 HScore≥175

ER Positive

ER Negative

Rb Positive

Rb Negative

Cyclin D1 Positive

Cyclin D1 Negative

p16 Positive

p16 Negative

p16 H-Score<175

p16 H-Score≥175

Ki67 ≤20%

Ki67 >20%

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. Here "Number Analyzed" signifies number of participants evaluable for specified rows.

PFS by Tumor Tissue Biomarkers Status, Including Genes (eg, Copy Numbers of CCND1, CDKN2A), Proteins (eg, Ki67, pRb), and RNA Expression (eg, cdk4, cdk6)

QTcS at 0 hour

QTcS at 2 hour

QTcS at 4 hour

QTcS at 6 hour

QTcS at 8 hour

QTcF at 0 hour

QTcF at 2 hour

QTcF at 4 hour

QTcF at 6 hour

QTcF at 8 hour

QTcB at 0 hour

QTcB at 2 hour

QTcB at 4 hour

QTcB at 6 hour

QTcB at 8 hour

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.

Corrected QT Interval (QTc) Time-matched Change From Baseline on Cycle 1 Day 14

Maximum QTcS <450 msec

Maximum QTcS 450-<480 msec

Maximum QTcS 480-<500 msec

Maximum QTcS ≥500 msec

Maximum QTcF <450 msec

Maximum QTcF 450-<480 msec

Maximum QTcF 480-<500 msec

Maximum QTcF ≥500 msec

Maximum QTcB <450 msec

Maximum QTcB 450-<480 msec

Maximum QTcB 480-<500 msec

Maximum QTcB ≥500 msec

Maximum QTcS Change <30 msec

Maximum QTcS 30≤Change <60 msec

Maximum QTcS Change≥60 msec

Maximum QTcF Change <30 msec

Maximum QTcF 30≤Change <60 msec

Maximum QTcF Change≥60 msec

Maximum QTcB Change <30 msec

Maximum QTcB 30≤Change <60 msec

Maximum QTcB Change≥60 msec

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.

Percentage of Participants With Corrected QT Interval (QTc)

Cycle 1 Day 14

Cycle 2 Day 14

Pharmacokinetic analysis set was a subset of AT participants, who were treated with Palbociclib and had at least one measured plasma concentration. Here "Number Analyzed" signifies number of participants evaluable for specified rows.

Observed Plasma Trough Concentration (Ctrough) at Steady-State

Patient Reported Outcome (PRO) Analysis Set is a subset of ITT participants, who had both baseline and at least one follow-up PRO assessment.

Change From Baseline Between Treatment Comparison in Euro Quality of Life (EQ-5D) Index

Change From Baseline Between Treatment Comparison in Functional Assessment of Cancer Therapy -Breast (FACT-B)

Participants with AEs

Participants with SAEs

Participants with Grade 3 or 4 AEs

Participants with Grade 5 AEs

Permanently discontinued study due to AEs

Permanently disc. palbociclib/placebo due to AEs

Permanently discontinued letrozole due to AEs

Temporarily disc. palbociclib/placebo due to AEs

Temporarily discontinued letrozole due to AEs

With palbociclib/placebo dose reduction due to AEs

AT population = ITT population because all the participants randomized were treated with study drugs per study design.

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities)

Overall Survival (OS)

1 year survival probability

2 year survival probability

3 year survival probability

Survival Probability at 1 Year, 2 Year and 3 Year

Anemia: Grade 1-2

Anemia: Grade 3

Hemoglobin Increased: Grade 1-2

Hemoglobin Increased: Grade 3

Neutrophils (Absolute): Grade 1-2

Neutrophils (Absolute): Grade 3

Neutrophils (Absolute): Grade 4

Platelets: Grade 1-2

Platelets: Grade 3

Platelets: Grade 4

White Blood Cells: Grade 1-2

White Blood Cells: Grade 3

White Blood Cells: Grade 4

ALT: Grade 1-2

ALT: Grade 3

ALT: Grade 4

Alkaline Phosphatase: Grade 1-2

Alkaline Phosphatase: Grade 3

AST: Grade 1-2

AST: Grade 3

Bilirubin (Total): Grade 1-2

Bilirubin (Total): Grade 3

Creatinine: Grade 1-2

Creatinine: Grade 3

Creatinine: Grade 4

Hypercalcemia: Grade 1-2

Hypercalcemia: Grade 3

Hyperkalemia: Grade 1-2

Hyperkalemia: Grade 3

Hyperkalemia: Grade 4

Hypermagnesemia: Grade 1-2

Hypermagnesemia: Grade 3

Hypermagnesemia: Grade 4

Hypernatremia: Grade 1-2

Hypernatremia: Grade 3

Hypoalbuminemia: Grade 1-2

Hypoalbuminemia: Grade 3

Hypocalcemia: Grade 1-2

Hypocalcemia: Grade 3

Hypocalcemia: Grade 4

Hypokalemia: Grade 1-2

Hypokalemia: Grade 3

Hypomagnesemia: Grade 1-2

Hypomagnesemia: Grade 3

Hypomagnesemia: Grade 4

Hyponatremia: Grade 1-2

Hyponatremia: Grade 3

AT population included all participants who received at least 1 dose of study medication, with treatment assignments designated according to actual study treatment received. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Number of Participants With Laboratory Abnormalities by Maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade

Overall Study

Palbociclib, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment in combination with Letrozole, 2.5mg, orally once daily (continuously)

Palbociclib, 125mg, orally once daily on Day 1 to Day 21 of every 28-day cycle followed by 7 days off treatment

The study is designed to compare the clinical benefit following treatment with letrozole in combination with Palbociclib versus letrozole in combination with placebo in Asian postmenopausal women with ER(+)/HER2(-) advanced breast cancer who have not received prior systemic anti cancer therapies for their advanced/metastatic disease.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Palbociclib (PD-0332991) + Letrozole vs. Letrozole For 1st Line Treatment Of Postmenopausal Women With ER+/HER2- Advanced Breast Cancer (PALOMA-2)	NCT01740427	Breast Neoplasm...	PD-0332991 Letrozole Placebo Letrozole	18 Years -	Pfizer
A Study Of Palbociclib (PD-0332991) + Letrozole VS. Placebo+ Letrozole For 1st Line Treatment Of Asian Postmenopausal Women With ER+/HER2- Advanced Breast Cancer [PALOMA-4]	NCT02297438	Breast Neoplasm...	Palbociclib Letrozole Placebo Letrozole	18 Years - 70 Years	Pfizer
A Study Of Palbociclib (PD-0332991) + Letrozole VS. Placebo+ Letrozole For 1st Line Treatment Of Asian Postmenopausal Women With ER+/HER2- Advanced Breast Cancer [PALOMA-4]	NCT02297438	Breast Neoplasm...	Palbociclib Letrozole Placebo Letrozole	18 Years - 70 Years	Pfizer

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