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

• ClinicalTrials.gov Identifier: NCT01684215
• Recruitment Status: Completed
• First Posted: September 12, 2012
• Results First Posted: May 2, 2017
• Last Update Posted: November 23, 2020
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Neoplasms; Breast Neoplasms
• Interventions: Drug: PD-0332991; Drug: letrozole
• Enrollment: 61

Participant Flow

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

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Period Title: Phase 1, Part 1
Started	6	6	0	0
Treated	6	6	0	0
Completed	0	0	0	0
Not Completed	6	6	0	0
Reason Not Completed
Adverse Event	1	0	0	0
Objective progression or relapse	5	6	0	0
Period Title: Phase 1, Part 2
Started	0	0	6 [1]	0
Completed	0	0	0	0
Not Completed	0	0	6	0
Reason Not Completed
Adverse Event	0	0	1	0
Commercial avaliabity of Palbociclib	0	0	4	0
Withdrawal by Subject	0	0	1	0
[1] Eligible participants who consented for Phase 1 Part 2.
Period Title: Phase 2
Started	0	0	0	43 [1]
Treated	0	0	0	42
Completed	0	0	0	0
Not Completed	0	0	0	43
Reason Not Completed
Death	0	0	0	8
Study terminated by sponsor	0	0	0	30
Enrolled but not treated	0	0	0	1
Lost to Follow-up	0	0	0	4
[1] Eligible participants who consented for Phase 2.

Baseline Characteristics

Arm/Group Title		PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort	Total
Arm/Group Description		In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	Total of all reporting groups
Overall Number of Baseline Participants		6	6	6	42	60
Baseline Analysis Population Description		Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	6 participants	6 participants	42 participants	60 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	4 66.7%	5 83.3%	4 66.7%	26 61.9%	39 65.0%
	>=65 years	2 33.3%	1 16.7%	2 33.3%	16 38.1%	21 35.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants	6 participants	6 participants	42 participants	60 participants
	Female	5 83.3%	2 33.3%	6 100.0%	42 100.0%	55 91.7%
	Male	1 16.7%	4 66.7%	0 0.0%	0 0.0%	5 8.3%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort
Arm/Group Description:	In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Overall Number of Participants Analyzed	6
Measure Type: Count of Participants; Unit of Measure: Participants
AEs	6 100.0%
SAEs	2 33.3%

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort
Arm/Group Description:	In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Overall Number of Participants Analyzed	6
Measure Type: Count of Participants; Unit of Measure: Participants
Grade 1	0 0.0%
Grade 2	0 0.0%
Grade 3	4 66.7%
Grade 4	2 33.3%
Grade 5	0 0.0%

4. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description:	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Overall Number of Participants Analyzed	42
Measure Type: Number; Number (90% Confidence Interval); Unit of Measure: percentage of participants
	75.6; (62.4 to 84.7)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description:	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Overall Number of Participants Analyzed	6	6	42
Measure Type: Count of Participants; Unit of Measure: Participants
AEs	6 100.0%	5 83.3%	42 100.0%
SAEs	0 0.0%	0 0.0%	2 4.8%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description:	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Overall Number of Participants Analyzed	6	6	42
Measure Type: Count of Participants; Unit of Measure: Participants
Grade 1	0 0.0%	1 16.7%	0 0.0%
Grade 2	0 0.0%	1 16.7%	2 4.8%
Grade 3	4 66.7%	3 50.0%	29 69.0%
Grade 4	2 33.3%	1 16.7%	10 23.8%
Grade 5	0 0.0%	0 0.0%	1 2.4%

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description:	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Overall Number of Participants Analyzed	6	6	6	42
Measure Type: Count of Participants; Unit of Measure: Participants
	6 100.0%	6 100.0%	6 100.0%	40 95.2%

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

18. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

19. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

20. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description:	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Overall Number of Participants Analyzed	6	6
Median (Full Range); Unit of Measure: ratio
	2.060; (1.81 to 3.54)	1.855; (1.74 to 3.10)

21. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description:	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Overall Number of Participants Analyzed	6	6
Median (Full Range); Unit of Measure: ratio
	1.130; (1.03 to 1.73)	1.105; (0.851 to 1.51)

22. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort
Arm/Group Description:	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Overall Number of Participants Analyzed	6	6
Median (Full Range); Unit of Measure: hour
Single dose	5.02; (3.97 to 8.02)	4.00; (3.90 to 8.00)
Multiple dose	4.02; (3.97 to 6.00)	4.02; (3.95 to 6.02)

23. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

24. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

25. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

26. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

27. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

28. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description:	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Overall Number of Participants Analyzed	6
Median (Full Range); Unit of Measure: hour
	4.90; (2.00 to 8.20)

29. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

30. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

31. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

32. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

33. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description:	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Overall Number of Participants Analyzed	20
Median (95% Confidence Interval); Unit of Measure: months
	41.4 [1]; (19.0 to NA)

[1]

Due to low number of participants with disease progression, upper limit of 95% confidence interval (CI) was not reached.

34. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

35. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

36. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description:	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Overall Number of Participants Analyzed	42
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (47.5 to NA)

[1]

Due to low number of participants with event, median and upper limit of 95% CI was not reached.

37. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description:		In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Overall Number of Participants Analyzed		42
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Baseline	Number Analyzed	42 participants
		106.46; (101.87 to 111.04)
Change at Cycle 2: Day 1	Number Analyzed	42 participants
		-1.20; (-4.56 to 2.16)
Change at Cycle 3: Day 1	Number Analyzed	41 participants
		-2.22; (-6.27 to 1.83)
Change at Cycle 5: Day 1	Number Analyzed	38 participants
		-2.38; (-6.07 to 1.31)
Change at Cycle 7: Day 1	Number Analyzed	35 participants
		-4.62; (-8.43 to -0.81)
Change at Cycle 9: Day 1	Number Analyzed	35 participants
		-4.45; (-7.86 to -1.04)
Change at Cycle 11: Day 1	Number Analyzed	33 participants
		-4.48; (-7.99 to -0.97)
Change at Cycle 13: Day 1	Number Analyzed	29 participants
		-6.32; (-10.56 to -2.09)
Change at Cycle 15: Day 1	Number Analyzed	28 participants
		-4.06; (-7.84 to -0.27)
Change at Cycle 17: Day 1	Number Analyzed	28 participants
		-6.07; (-9.48 to -2.65)
Change at Cycle 19: Day 1	Number Analyzed	27 participants
		-7.39; (-12.06 to -2.72)
Change at Cycle 21: Day 1	Number Analyzed	27 participants
		-5.85; (-10.29 to -1.42)
Change at Cycle 23: Day 1	Number Analyzed	26 participants
		-5.89; (-10.97 to -0.82)
Change at Cycle 25: Day 1	Number Analyzed	24 participants
		-4.22; (-8.61 to 0.17)
Change at Cycle 27: Day 1	Number Analyzed	24 participants
		-4.76; (-9.22 to -0.30)
Change at Cycle 29: Day 1	Number Analyzed	23 participants
		-6.26; (-10.94 to -1.57)
Change at Cycle 31: Day 1	Number Analyzed	21 participants
		-5.13; (-9.46 to -0.79)
Change at Cycle 33: Day 1	Number Analyzed	20 participants
		-7.12; (-11.14 to -3.11)
Change at Cycle 35: Day 1	Number Analyzed	20 participants
		-7.68; (-11.66 to -3.70)
Change at Cycle 37: Day 1	Number Analyzed	19 participants
		-8.07; (-12.56 to -3.58)
Change at Cycle 39: Day 1	Number Analyzed	15 participants
		-6.87; (-10.89 to -2.85)
Change at Cycle 41: Day 1	Number Analyzed	11 participants
		-5.70; (-11.41 to 0.02)
Change at Cycle 43: Day 1	Number Analyzed	6 participants
		-10.42; (-17.24 to -3.59)
Change at Cycle 45: Day 1	Number Analyzed	3 participants
		-7.94; (-26.09 to 10.20)
Change at Cycle 47: Day 1	Number Analyzed	3 participants
		-8.56; (-22.48 to 5.36)
Change at Cycle 49: Day 1	Number Analyzed	2 participants
		-10.58; (-66.70 to 45.54)
End of Treatment	Number Analyzed	39 participants
		-9.17; (-13.82 to -4.52)

38. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description:		In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Overall Number of Participants Analyzed		42
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Baseline	Number Analyzed	42 participants
		80.22; (76.21 to 84.23)
Change at Cycle 2: Day 1	Number Analyzed	42 participants
		-1.15; (-4.10 to 1.80)
Change at Cycle 3: Day 1	Number Analyzed	41 participants
		-1.34; (-4.72 to 2.04)
Change at Cycle 5: Day 1	Number Analyzed	38 participants
		-0.36; (-3.21 to 2.48)
Change at Cycle 7: Day 1	Number Analyzed	35 participants
		-3.56; (-6.52 to -0.60)
Change at Cycle 9: Day 1	Number Analyzed	35 participants
		-2.39; (-4.94 to 0.16)
Change at Cycle 11: Day 1	Number Analyzed	33 participants
		-3.94; (-6.79 to -1.09)
Change at Cycle 13: Day 1	Number Analyzed	29 participants
		-4.74; (-8.11 to -1.37)
Change at Cycle 15: Day 1	Number Analyzed	28 participants
		-2.98; (-6.23 to 0.26)
Change at Cycle 17: Day 1	Number Analyzed	28 participants
		-4.64; (-7.37 to -1.91)
Change at Cycle 19: Day 1	Number Analyzed	27 participants
		-5.48; (-8.94 to -2.01)
Change at Cycle 21: Day 1	Number Analyzed	27 participants
		-4.34; (-7.94 to -0.74)
Change at Cycle 23: Day 1	Number Analyzed	26 participants
		-4.39; (-8.42 to -0.37)
Change at Cycle 25: Day 1	Number Analyzed	24 participants
		-3.22; (-6.94 to 0.50)
Change at Cycle 27: Day 1	Number Analyzed	24 participants
		-3.80; (-7.34 to -0.26)
Change at Cycle 29: Day 1	Number Analyzed	23 participants
		-4.52; (-8.58 to -0.45)
Change at Cycle 31: Day 1	Number Analyzed	21 participants
		-4.55; (-8.27 to -0.84)
Change at Cycle 33: Day 1	Number Analyzed	20 participants
		-6.67; (-10.26 to -3.08)
Change at Cycle 35: Day 1	Number Analyzed	20 participants
		-6.63; (-10.38 to -2.88)
Change at Cycle 37: Day 1	Number Analyzed	19 participants
		-6.49; (-10.52 to -2.46)
Change at Cycle 39: Day 1	Number Analyzed	15 participants
		-5.07; (-8.37 to -1.76)
Change at Cycle 41: Day 1	Number Analyzed	11 participants
		-5.06; (-9.92 to -0.20)
Change at Cycle 43: Day 1	Number Analyzed	6 participants
		-7.08; (-14.53 to 0.37)
Change at Cycle 45: Day 1	Number Analyzed	3 participants
		-5.94; (-27.36 to 15.47)
Change at Cycle 47: Day 1	Number Analyzed	3 participants
		-6.22; (-25.11 to 12.66)
Change at Cycle 49: Day 1	Number Analyzed	2 participants
		-8.58; (-90.11 to 72.95)
End of Treatment	Number Analyzed	39 participants
		-7.09; (-10.98 to -3.20)

39. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description:		In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
Overall Number of Participants Analyzed		42
Mean (95% Confidence Interval); Unit of Measure: units on a scale
Baseline	Number Analyzed	42 participants
		71.52; (68.36 to 74.69)
Change at Cycle 2: Day 1	Number Analyzed	42 participants
		-1.17; (-3.24 to 0.89)
Change at Cycle 3: Day 1	Number Analyzed	41 participants
		-2.20; (-4.74 to 0.35)
Change at Cycle 5: Day 1	Number Analyzed	38 participants
		-2.54; (-5.25 to 0.16)
Change at Cycle 7: Day 1	Number Analyzed	35 participants
		-3.63; (-6.44 to -0.82)
Change at Cycle 9: Day 1	Number Analyzed	35 participants
		-3.31; (-6.03 to -0.60)
Change at Cycle 11: Day 1	Number Analyzed	33 participants
		-2.30; (-5.06 to 0.45)
Change at Cycle 13: Day 1	Number Analyzed	29 participants
		-3.93; (-7.31 to -0.56)
Change at Cycle 15: Day 1	Number Analyzed	28 participants
		-2.49; (-5.09 to 0.11)
Change at Cycle 17: Day 1	Number Analyzed	28 participants
		-3.18; (-6.02 to -0.34)
Change at Cycle 19: Day 1	Number Analyzed	27 participants
		-4.32; (-8.01 to -0.63)
Change at Cycle 21: Day 1	Number Analyzed	27 participants
		-3.56; (-6.83 to -0.28)
Change at Cycle 23: Day 1	Number Analyzed	26 participants
		-3.19; (-7.11 to 0.73)
Change at Cycle 25: Day 1	Number Analyzed	24 participants
		-2.13; (-5.51 to 1.26)
Change at Cycle 27: Day 1	Number Analyzed	24 participants
		-2.50; (-5.77 to 0.77)
Change at Cycle 29: Day 1	Number Analyzed	23 participants
		-3.70; (-7.36 to -0.03)
Change at Cycle 31: Day 1	Number Analyzed	21 participants
		-1.95; (-5.23 to 1.33)
Change at Cycle 33: Day 1	Number Analyzed	20 participants
		-4.30; (-7.65 to -0.95)
Change at Cycle 35: Day 1	Number Analyzed	20 participants
		-4.65; (-8.68 to -0.62)
Change at Cycle 37: Day 1	Number Analyzed	19 participants
		-4.84; (-8.77 to -0.92)
Change at Cycle 39: Day 1	Number Analyzed	15 participants
		-3.47; (-7.09 to 0.15)
Change at Cycle 41: Day 1	Number Analyzed	11 participants
		-2.27; (-7.62 to 3.08)
Change at Cycle 43: Day 1	Number Analyzed	6 participants
		-7.00; (-13.83 to -0.17)
Change at Cycle 45: Day 1	Number Analyzed	3 participants
		-3.00; (-22.40 to 16.40)
Change at Cycle 47: Day 1	Number Analyzed	3 participants
		-4.00; (-12.96 to 4.96)
Change at Cycle 49: Day 1	Number Analyzed	2 participants
		-2.00; (-14.71 to 10.71)
End of Treatment	Number Analyzed	39 participants
		-6.03; (-9.61 to -2.45)

40. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

41. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

Adverse Events

Time Frame	Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (up to 308 days), Part 2 Phase 1: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1526 days)
Adverse Event Reporting Description	Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non serious in another participant, or 1 participant may have experienced both a serious and non serious event during the study. Safety analysis set included all enrolled participants who received at least 1 dose of study drug (PD-0332991).
Arm/Group Title	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Arm/Group Description	In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase1-Part 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.	In Phase 2, participants received Letrozole 2.5 mg tablet along with PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
All-Cause Mortality
	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--
Serious Adverse Events
	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/6 (0.00%)	0/6 (0.00%)	2/6 (33.33%)	4/42 (9.52%)
Blood and lymphatic system disorders
Febrile Neutropenia * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	1/42 (2.38%)
Cardiac disorders
Supraventricular tachycardia * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Gastrointestinal disorders
Gastrointestinal perforation * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Vomiting * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	1/42 (2.38%)
General disorders
Malaise * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	1/42 (2.38%)
Musculoskeletal and connective tissue disorders
Osteoarthritis * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	1/42 (2.38%)
Nervous system disorders
Cerebral Haemorrhage * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	1/42 (2.38%)
Dizziness * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	1/42 (2.38%)
Subarachnoid Haemorrhage * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	1/42 (2.38%)
* Indicates events were collected by non-systematic assessment; [1] MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	PD-0332991 100 mg: Dose Escalation Cohort	PD-0332991 125 mg: Dose Escalation Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort	PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	6/6 (100.00%)	6/6 (100.00%)	6/6 (100.00%)	42/42 (100.00%)
Blood and lymphatic system disorders
Anaemia * [1]	0/6 (0.00%)	2/6 (33.33%)	0/6 (0.00%)	10/42 (23.81%)
Leukopenia * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	5/42 (11.90%)
Neutropenia * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	9/42 (21.43%)
Cardiac disorders
Palpitations * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	4/42 (9.52%)
Mitral valve incompetence * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Supraventricular tachycardia * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Eye disorders
Conjunctival haemorrhage * [1]	0/6 (0.00%)	0/6 (0.00%)	2/6 (33.33%)	2/42 (4.76%)
Lacrimation increased * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	1/42 (2.38%)
Macular oedema * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Vision blurred * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Gastrointestinal disorders
Constipation * [1]	1/6 (16.67%)	2/6 (33.33%)	2/6 (33.33%)	12/42 (28.57%)
Nausea * [1]	1/6 (16.67%)	1/6 (16.67%)	2/6 (33.33%)	9/42 (21.43%)
Stomatitis * [1]	0/6 (0.00%)	2/6 (33.33%)	1/6 (16.67%)	32/42 (76.19%)
Vomiting * [1]	1/6 (16.67%)	0/6 (0.00%)	1/6 (16.67%)	5/42 (11.90%)
Cheilitis * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	5/42 (11.90%)
Dental caries * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	4/42 (9.52%)
Diarrhoea * [1]	1/6 (16.67%)	4/6 (66.67%)	4/6 (66.67%)	5/42 (11.90%)
Abdominal discomfort * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Abdominal distension * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Abdominal pain upper * [1]	1/6 (16.67%)	0/6 (0.00%)	2/6 (33.33%)	1/42 (2.38%)
Food poisoning * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Glossitis * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	1/42 (2.38%)
Abdominal pain * [1]	0/6 (0.00%)	1/6 (16.67%)	0/6 (0.00%)	0/42 (0.00%)
Anal haemorrhage * [1]	0/6 (0.00%)	1/6 (16.67%)	0/6 (0.00%)	0/42 (0.00%)
Dyspepsia * [1]	1/6 (16.67%)	0/6 (0.00%)	0/6 (0.00%)	0/42 (0.00%)
Gastritis * [1]	0/6 (0.00%)	1/6 (16.67%)	0/6 (0.00%)	3/42 (7.14%)
General disorders
Malaise * [1]	2/6 (33.33%)	0/6 (0.00%)	0/6 (0.00%)	9/42 (21.43%)
Influenza like illness * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	5/42 (11.90%)
Pain * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	3/42 (7.14%)
Pyrexia * [1]	0/6 (0.00%)	1/6 (16.67%)	2/6 (33.33%)	3/42 (7.14%)
Chest discomfort * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Fatigue * [1]	0/6 (0.00%)	2/6 (33.33%)	2/6 (33.33%)	2/42 (4.76%)
Mucosal inflammation * [1]	0/6 (0.00%)	0/6 (0.00%)	2/6 (33.33%)	1/42 (2.38%)
Oedema peripheral * [1]	1/6 (16.67%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
General physical health deterioration * [1]	1/6 (16.67%)	0/6 (0.00%)	0/6 (0.00%)	0/42 (0.00%)
Non-cardiac chest pain * [1]	0/6 (0.00%)	1/6 (16.67%)	0/6 (0.00%)	0/42 (0.00%)
Immune system disorders
Seasonal allergy * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Infections and infestations
Nasopharyngitis * [1]	1/6 (16.67%)	0/6 (0.00%)	2/6 (33.33%)	19/42 (45.24%)
Upper respiratory tract infection * [1]	0/6 (0.00%)	0/6 (0.00%)	2/6 (33.33%)	6/42 (14.29%)
Angular cheilitis * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	4/42 (9.52%)
Cellulitis * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	4/42 (9.52%)
Conjunctivitis * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	4/42 (9.52%)
Oral herpes * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	3/42 (7.14%)
Pharyngitis * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	8/42 (19.05%)
Influenza * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	1/42 (2.38%)
Skin infection * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Urinary tract infection * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	1/42 (2.38%)
Cystitis * [1]	1/6 (16.67%)	0/6 (0.00%)	0/6 (0.00%)	2/42 (4.76%)
Lung infection * [1]	1/6 (16.67%)	0/6 (0.00%)	0/6 (0.00%)	0/42 (0.00%)
Injury, poisoning and procedural complications
Fall * [1]	0/6 (0.00%)	0/6 (0.00%)	4/6 (66.67%)	9/42 (21.43%)
Contusion * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	3/42 (7.14%)
Femur fracture * [1]	1/6 (16.67%)	0/6 (0.00%)	0/6 (0.00%)	0/42 (0.00%)
Investigations
Alanine aminotransferase increased * [1]	1/6 (16.67%)	1/6 (16.67%)	2/6 (33.33%)	12/42 (28.57%)
Aspartate aminotransferase increased * [1]	2/6 (33.33%)	1/6 (16.67%)	2/6 (33.33%)	11/42 (26.19%)
Neutrophil count decreased * [1]	5/6 (83.33%)	4/6 (66.67%)	6/6 (100.00%)	34/42 (80.95%)
Platelet count decreased * [1]	1/6 (16.67%)	2/6 (33.33%)	4/6 (66.67%)	9/42 (21.43%)
Weight decreased * [1]	1/6 (16.67%)	1/6 (16.67%)	1/6 (16.67%)	5/42 (11.90%)
White blood cell count decreased * [1]	4/6 (66.67%)	5/6 (83.33%)	6/6 (100.00%)	30/42 (71.43%)
Blood creatinine increased * [1]	2/6 (33.33%)	0/6 (0.00%)	1/6 (16.67%)	2/42 (4.76%)
Activated partial thromboplastin time prolonged * [1]	0/6 (0.00%)	1/6 (16.67%)	0/6 (0.00%)	0/42 (0.00%)
Blood alkaline phosphatase increased * [1]	2/6 (33.33%)	2/6 (33.33%)	0/6 (0.00%)	0/42 (0.00%)
Blood bilirubin increased * [1]	1/6 (16.67%)	0/6 (0.00%)	0/6 (0.00%)	0/42 (0.00%)
Electrocardiogram QT prolonged * [1]	1/6 (16.67%)	0/6 (0.00%)	0/6 (0.00%)	0/42 (0.00%)
Gamma-glutamyltransferase increased * [1]	1/6 (16.67%)	0/6 (0.00%)	0/6 (0.00%)	0/42 (0.00%)
Lymphocyte count decreased * [1]	1/6 (16.67%)	3/6 (50.00%)	0/6 (0.00%)	2/42 (4.76%)
Metabolism and nutrition disorders
Decreased appetite * [1]	1/6 (16.67%)	0/6 (0.00%)	1/6 (16.67%)	6/42 (14.29%)
Hypocalcaemia * [1]	1/6 (16.67%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Hypoglycaemia * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Hypercalcaemia * [1]	0/6 (0.00%)	1/6 (16.67%)	0/6 (0.00%)	0/42 (0.00%)
Hypermagnesaemia * [1]	1/6 (16.67%)	0/6 (0.00%)	0/6 (0.00%)	0/42 (0.00%)
Hypoalbuminaemia * [1]	0/6 (0.00%)	1/6 (16.67%)	0/6 (0.00%)	0/42 (0.00%)
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	4/42 (9.52%)
Myalgia * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	4/42 (9.52%)
Arthralgia * [1]	1/6 (16.67%)	0/6 (0.00%)	0/6 (0.00%)	5/42 (11.90%)
Osteoporosis * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	3/42 (7.14%)
Pain in extremity * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	4/42 (9.52%)
Back pain * [1]	1/6 (16.67%)	1/6 (16.67%)	1/6 (16.67%)	2/42 (4.76%)
Muscle spasms * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	1/42 (2.38%)
Neck pain * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	1/42 (2.38%)
Musculoskeletal chest pain * [1]	1/6 (16.67%)	0/6 (0.00%)	0/6 (0.00%)	1/42 (2.38%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain * [1]	0/6 (0.00%)	1/6 (16.67%)	0/6 (0.00%)	1/42 (2.38%)
Tumour pain * [1]	0/6 (0.00%)	1/6 (16.67%)	0/6 (0.00%)	0/42 (0.00%)
Nervous system disorders
Dysgeusia * [1]	1/6 (16.67%)	0/6 (0.00%)	1/6 (16.67%)	4/42 (9.52%)
Headache * [1]	0/6 (0.00%)	1/6 (16.67%)	2/6 (33.33%)	7/42 (16.67%)
Dizziness * [1]	0/6 (0.00%)	1/6 (16.67%)	0/6 (0.00%)	3/42 (7.14%)
Parosmia * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Peripheral sensory neuropathy * [1]	1/6 (16.67%)	0/6 (0.00%)	2/6 (33.33%)	0/42 (0.00%)
Sensory disturbance * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	1/42 (2.38%)
Dysaesthesia * [1]	1/6 (16.67%)	0/6 (0.00%)	0/6 (0.00%)	0/42 (0.00%)
Psychiatric disorders
Anxiety disorder * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Insomnia * [1]	1/6 (16.67%)	1/6 (16.67%)	1/6 (16.67%)	0/42 (0.00%)
Anxiety * [1]	0/6 (0.00%)	1/6 (16.67%)	0/6 (0.00%)	0/42 (0.00%)
Renal and urinary disorders
Calculus urinary * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Proteinuria * [1]	0/6 (0.00%)	1/6 (16.67%)	0/6 (0.00%)	0/42 (0.00%)
Reproductive system and breast disorders
Genital haemorrhage * [1]	1/6 (16.67%)	0/6 (0.00%)	0/6 (0.00%)	0/42 (0.00%)
Respiratory, thoracic and mediastinal disorders
Epistaxis * [1]	0/6 (0.00%)	1/6 (16.67%)	0/6 (0.00%)	6/42 (14.29%)
Oropharyngeal pain * [1]	1/6 (16.67%)	0/6 (0.00%)	0/6 (0.00%)	4/42 (9.52%)
Asthma * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Cough * [1]	1/6 (16.67%)	0/6 (0.00%)	1/6 (16.67%)	2/42 (4.76%)
Dysphonia * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Rhinitis allergic * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	1/42 (2.38%)
Upper respiratory tract inflammation * [1]	0/6 (0.00%)	0/6 (0.00%)	2/6 (33.33%)	1/42 (2.38%)
Upper-airway cough syndrome * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	0/42 (0.00%)
Skin and subcutaneous tissue disorders
Alopecia * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	8/42 (19.05%)
Dry skin * [1]	2/6 (33.33%)	0/6 (0.00%)	0/6 (0.00%)	4/42 (9.52%)
Rash * [1]	1/6 (16.67%)	0/6 (0.00%)	1/6 (16.67%)	8/42 (19.05%)
Eczema * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	3/42 (7.14%)
Dermatitis acneiform * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	3/42 (7.14%)
Nail disorder * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	3/42 (7.14%)
Pruritus * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	4/42 (9.52%)
Rash maculo-papular * [1]	1/6 (16.67%)	0/6 (0.00%)	0/6 (0.00%)	3/42 (7.14%)
Dermal cyst * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	1/42 (2.38%)
Haemorrhage subcutaneous * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	1/42 (2.38%)
Palmar-plantar erythrodysaesthesia syndrome * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	2/42 (4.76%)
Vascular disorders
Hypertension * [1]	0/6 (0.00%)	0/6 (0.00%)	1/6 (16.67%)	5/42 (11.90%)
Hot Flush * [1]	0/6 (0.00%)	0/6 (0.00%)	0/6 (0.00%)	3/42 (7.14%)
* Indicates events were collected by non-systematic assessment; [1] MedDRA v17.1 was used for Dose Escalation Cohorts. MedDRA v20.1 was used for MTD Cohort. MedDRA v21.1 was used for Expanded Cohort.

Limitations and Caveats

[Not Specified]

More Information

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

• 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):

Takahashi M, Masuda N, Nishimura R, Inoue K, Ohno S, Iwata H, Hashigaki S, Muramatsu Y, Umeyama Y, Toi M. Palbociclib-letrozole as first-line treatment for advanced breast cancer: Updated results from a Japanese phase 2 study. Cancer Med. 2020 Jul;9(14):4929-4940. doi: 10.1002/cam4.3091. Epub 2020 May 18.

Masuda N, Mukai H, Inoue K, Rai Y, Ohno S, Mori Y, Hashigaki S, Muramatsu Y, Umeyama Y, Iwata H, Toi M. Neutropenia management with palbociclib in Japanese patients with advanced breast cancer. Breast Cancer. 2019 Sep;26(5):637-650. doi: 10.1007/s12282-019-00970-7. Epub 2019 May 24. Erratum In: Breast Cancer. 2019 Jun 5;:

Tamura K, Mukai H, Naito Y, Yonemori K, Kodaira M, Tanabe Y, Yamamoto N, Osera S, Sasaki M, Mori Y, Hashigaki S, Nagasawa T, Umeyama Y, Yoshino T. Phase I study of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, in Japanese patients. Cancer Sci. 2016 Jun;107(6):755-63. doi: 10.1111/cas.12932. Epub 2016 May 11.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01684215
• Other Study ID Numbers: A5481010
• First Submitted: September 10, 2012
• First Posted: September 12, 2012
• Results First Submitted: November 9, 2016
• Results First Posted: May 2, 2017
• Last Update Posted: November 23, 2020