2.5 mg , orally once daily (continuously)

Kel for palbociclib in the single-dose part (lead-in phase) was obtained by linear regression of the log-linear concentration-time curve.

MRT for palbociclib in the single-dose part (lead-in phase) was calculated as AUMCinf/AUCinf, where AUMCinf was area under the first moment curve from time 0 to infinity.

t1/2 for palbociclib in the single-dose part (lead-in phase) was calculated as Loge(2)/kel.

CL/F for palbociclib in the single-dose part (lead-in phase) was calculated as Dose/AUCinf.

Vz/F for palbociclib in the single-dose part (lead-in phase) was calculated as Dose/(AUCinf * kel).

Css,max of palbociclib in the multiple-dose part (Cycle 1) was observed directly from data.

Css,min of palbociclib in the multiple-dose part (Cycle 1) was observed directly from data.

AUCss,tau of palbociclib in the multiple-dose part (Cycle 1) was determined by linear/log trapezoidal method.

Css,av of palbociclib in the multiple-dose part (Cycle 1) was calculated as AUCss,tau/tau, where tau was 24 hours.

Tss,max of palbociclib in the multiple-dose part (Cycle 1) was observed directly from data as time of first occurrence within tau (=24 hours) at steady state.

Vz/F of palbociclib in the multiple-dose part (Cycle 1) was calculated as Dose/(AUCss,tau * kel), where AUCss,tau was the AUC within a dosing interval of tau (=24 hours) at steady state and kel was the terminal phase rate constant following multiple-dose calculated by a linear regression of the log-linear concentration-time curve.

t1/2 of palbociclib in the multiple-dose part (Cycle 1) was calculated as ln (2)/kel, where kel was the terminal phase rate constant following multiple-dose calculated by a linear regression of the log-linear concentration-time curve.

CL/F of palbociclib in the multiple-dose part (Cycle 1) was calculated as Dose/AUCss,tau, where AUCss,tau was the AUC within a dosing interval of tau (=24 hours) at steady state.

PTF of palbociclib in the multiple-dose part (Cycle 1) was determined as (Css,max - Css,min)/Css,av. Css,max and Css,min were observed directly from data while Css,av was calculated as AUCss,tau/tau, where tau was 24 hours.

Rac of palbociclib was determined as AUCss,tau/AUCsd,tau, where AUCss,tau (tau=24 hours) was from multiple-dose part (Cycle 1) and AUCsd,tau was AUC24 from single-dose part (lead-in phase).

Rss of palbociclib was calculated as AUCss,tau/AUCinf, where AUCss,tau (tau=24 hours) was from multiple-dose part (Cycle 1) and AUCinf was from single-dose part (lead-in phase).

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of investigational product administration. AEs included both SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. AEs were graded by NCI CTCAE version 4.0: Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.

The number of participants with the following laboratory test abnormalities meeting any of the Grades 1 to 4 criteria per the NCI CTCAE (version 4.0) is summarized: anemia, lymphopenia, neutropenia, platelet count decreased, white blood cell (WBC) decreased, alanine aminotransferase (ALT) increased, alkaline phosphatase increased, aspartate aminotransferase (AST) increased, bilirubin (total) increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, and hyponatremia. Grade 1=mild, Grade 2=moderate, Grade 3=severe and Grade 4=life-threatening. One participant might had more than 1 laboratory test abnormality.

QT interval (time from electrocardiogram [ECG] Q wave and the end of the T wave corresponding to electrical systole) corrected for heart rate using Fridericia's formula was QTcF and QT interval corrected for heart rate using Bazett's formula was QTcB. Categorical summarization criteria for QTcF and QTcB were as follows: 1) maximum absolute value of <450 milliseconds (msec), >=450 to <=480 msec, >=481 to <=500 msec, or >=500 msec; 2) maximum increase from baseline of <30 msec, >=30 to <60 msec, or >=60 msec. One participant could be reported under more than 1 categorical summarization criteria for QTcF and QTcB Parameters.

PFS was defined as the time from Cycle 1 Day 1 (C1D1) to date of first documentation of disease progression (PD) or death due to any cause, whichever occurred first. Documentation of progression was by objective disease assessment as defined by the Response Evaluation Criteria in Solid Tumor (RECIST) (version 1.1). PD was defined as a >=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 millimeter (mm); or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new unequivocal malignant lesions. Median PFS was estimated using the Kaplan-Meier method.

ORR was the percentage of participants with an objective response (complete response [CR] or partial response [PR]). Per RECIST (version 1.1). CR: complete disappearance of all target lesions except nodal disease or disappearance of all non-target lesions and normalization of tumor marker levels. All target nodes/lymph nodes must decrease to normal size (<10 mm short axis); PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions (short diameter=sum for target nodes; longest diameter=sum for all other target lesions). PD: 20% increase in sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions.

Disease control (DC) = CR, PR or stable disease (SD) >= 24 weeks according to RECIST version 1.1 recorded from C1D1 until disease progression or death due to any cause. CR: complete disappearance of all target lesions except nodal disease or disappearance of all non-target lesions and normalization of tumor marker levels. All target nodes/lymph nodes must decrease to normal size (<10 mm short axis); PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions (short diameter=sum for target nodes; longest diameter=sum for all other target lesions). SD: Does not qualify for CR, PR or progression. PD: 20% increase in sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm or appearance of new unequivocal malignant lesions.

Duration of response was the time from first documentation of CR or PR to date of first documentation of PD or death for the participants with an objective response (CR or PR). Per RECIST (version 1.1). CR: complete disappearance of all target lesions except nodal disease or disappearance of all non-target lesions and normalization of tumor marker levels. All target nodes/lymph nodes must decrease to normal size (<10 mm short axis); PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions (short diameter=sum for target nodes; longest diameter=sum for all other target lesions). PD: 20% increase in sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions. Kaplan-Meier method was used.

PFS was defined as the time from C1D1 to date of first documentation of PD or death due to any cause, whichever occurred first. Documentation of progression was by objective disease assessment as defined by the RECIST (version 1.1). PD was defined as a >=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 millimeter (mm); or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new unequivocal malignant lesions. One-year PFS probability was defined as the probability (expressed as percentage) of PFS at 1 year after C1D1. PFS probability was determined using the Kaplan-Meier method.

Plasma samples were analyzed for letrozole concentrations using a validated, sensitive and specific high-performance liquid chromatography tandem mass spectrometric (HPLC/MS/MS) method.

The pRb was one of the skin biomarkers and samples were assayed using immunohistochemistry (IHC) method. Ratio over baseline was calculated by dividing the H-score value for pRb at each specified time point by baseline value. The H-score value, which could range from 0 to 300 (strongest expression) with higher score representing stronger expression, was calculated from the total of each individual intensity of staining (0 [negative], 1+ [weak], 2+ [moderate], 3+ [strong]) multiplied by the percentages of cells (0 to 100) that represented that staining.

The Ki67 was one of the skin biomarkers and samples were assayed using IHC method. Ratio over baseline was calculated by dividing the percentage of Ki67 positive cells at each specified time point by baseline value.

Blood samples were collected to provide serum for the assessments of TK activity. The concentrations of TK were determined using enzyme-linked immunosorbent assay (ELISA) method. Ratio of serum TK concentration at each specified time point over baseline value was presented.

Tmax for palbociclib in the single-dose part (lead-in phase) was observed directly from data as time of first occurrence.

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.

AUC10 for palbociclib in the single-dose part (lead-in phase) was obtained by linear/log trapezoidal method.

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.

AUC24 is AUCtau, where the dosing interval (tau) is 24 hours. AUC24 in the single-dose part (lead-in phase) for palbociclib was obtained by linear/log trapezoidal method.

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.

AUClast for palbociclib in the single-dose part (lead-in phase) was obtained by linear/log trapezoidal method.

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.

AUCinf for palbociclib in the single-dose part (lead-in phase) was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the rate constant for terminal phase obtained by linear regression of the log-linear concentration-time curve.

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.

Kel for palbociclib in the single-dose part (lead-in phase) was obtained by linear regression of the log-linear concentration-time curve.

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.

MRT for palbociclib in the single-dose part (lead-in phase) was calculated as AUMCinf/AUCinf, where AUMCinf was area under the first moment curve from time 0 to infinity.

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.

t1/2 for palbociclib in the single-dose part (lead-in phase) was calculated as Loge(2)/kel.

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.

CL/F for palbociclib in the single-dose part (lead-in phase) was calculated as Dose/AUCinf.

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.

Vz/F for palbociclib in the single-dose part (lead-in phase) was calculated as Dose/(AUCinf * kel).

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose part.

Css,max of palbociclib in the multiple-dose part (Cycle 1) was observed directly from data.

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the multiple-dose part.

Css,min of palbociclib in the multiple-dose part (Cycle 1) was observed directly from data.

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the multiple-dose part.

AUCss,tau of palbociclib in the multiple-dose part (Cycle 1) was determined by linear/log trapezoidal method.

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the multiple-dose part.

Css,av of palbociclib in the multiple-dose part (Cycle 1) was calculated as AUCss,tau/tau, where tau was 24 hours.

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the multiple-dose part.

Tss,max of palbociclib in the multiple-dose part (Cycle 1) was observed directly from data as time of first occurrence within tau (=24 hours) at steady state.

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the multiple-dose part.

Vz/F of palbociclib in the multiple-dose part (Cycle 1) was calculated as Dose/(AUCss,tau * kel), where AUCss,tau was the AUC within a dosing interval of tau (=24 hours) at steady state and kel was the terminal phase rate constant following multiple-dose calculated by a linear regression of the log-linear concentration-time curve.

All enrolled and treated participants who had at least 1 PK parameter of primary interest and a well characterized terminal phase in the multiple-dose part.

t1/2 of palbociclib in the multiple-dose part (Cycle 1) was calculated as ln (2)/kel, where kel was the terminal phase rate constant following multiple-dose calculated by a linear regression of the log-linear concentration-time curve.

All enrolled and treated participants who had at least 1 PK parameter of primary interest and a well characterized terminal phase in the multiple-dose part .

CL/F of palbociclib in the multiple-dose part (Cycle 1) was calculated as Dose/AUCss,tau, where AUCss,tau was the AUC within a dosing interval of tau (=24 hours) at steady state.

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the multiple-dose part.

PTF of palbociclib in the multiple-dose part (Cycle 1) was determined as (Css,max - Css,min)/Css,av. Css,max and Css,min were observed directly from data while Css,av was calculated as AUCss,tau/tau, where tau was 24 hours.

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the multiple-dose part.

Rac of palbociclib was determined as AUCss,tau/AUCsd,tau, where AUCss,tau (tau=24 hours) was from multiple-dose part (Cycle 1) and AUCsd,tau was AUC24 from single-dose part (lead-in phase).

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose and multiple-dose part.

Rss of palbociclib was calculated as AUCss,tau/AUCinf, where AUCss,tau (tau=24 hours) was from multiple-dose part (Cycle 1) and AUCinf was from single-dose part (lead-in phase).

All enrolled and treated participants who had at least 1 PK parameter of primary interest in the single-dose and multiple-dose part.

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of investigational product administration. AEs included both SAEs and non-serious AEs. Causality to study treatment was determined by the investigator.

Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of investigational product administration. AEs included both SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. AEs were graded by NCI CTCAE version 4.0: Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.

Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

The number of participants with the following laboratory test abnormalities meeting any of the Grades 1 to 4 criteria per the NCI CTCAE (version 4.0) is summarized: anemia, lymphopenia, neutropenia, platelet count decreased, white blood cell (WBC) decreased, alanine aminotransferase (ALT) increased, alkaline phosphatase increased, aspartate aminotransferase (AST) increased, bilirubin (total) increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, and hyponatremia. Grade 1=mild, Grade 2=moderate, Grade 3=severe and Grade 4=life-threatening. One participant might had more than 1 laboratory test abnormality.

Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

QT interval (time from electrocardiogram [ECG] Q wave and the end of the T wave corresponding to electrical systole) corrected for heart rate using Fridericia's formula was QTcF and QT interval corrected for heart rate using Bazett's formula was QTcB. Categorical summarization criteria for QTcF and QTcB were as follows: 1) maximum absolute value of <450 milliseconds (msec), >=450 to <=480 msec, >=481 to <=500 msec, or >=500 msec; 2) maximum increase from baseline of <30 msec, >=30 to <60 msec, or >=60 msec. One participant could be reported under more than 1 categorical summarization criteria for QTcF and QTcB Parameters.

Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

PFS was defined as the time from Cycle 1 Day 1 (C1D1) to date of first documentation of disease progression (PD) or death due to any cause, whichever occurred first. Documentation of progression was by objective disease assessment as defined by the Response Evaluation Criteria in Solid Tumor (RECIST) (version 1.1). PD was defined as a >=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 millimeter (mm); or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new unequivocal malignant lesions. Median PFS was estimated using the Kaplan-Meier method.

Efficacy analysis set included all enrolled participants who started the treatment of Cycle 1.

ORR was the percentage of participants with an objective response (complete response [CR] or partial response [PR]). Per RECIST (version 1.1). CR: complete disappearance of all target lesions except nodal disease or disappearance of all non-target lesions and normalization of tumor marker levels. All target nodes/lymph nodes must decrease to normal size (<10 mm short axis); PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions (short diameter=sum for target nodes; longest diameter=sum for all other target lesions). PD: 20% increase in sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions.

Efficacy analysis set included all enrolled participants who started the treatment of Cycle 1.

Disease control (DC) = CR, PR or stable disease (SD) >= 24 weeks according to RECIST version 1.1 recorded from C1D1 until disease progression or death due to any cause. CR: complete disappearance of all target lesions except nodal disease or disappearance of all non-target lesions and normalization of tumor marker levels. All target nodes/lymph nodes must decrease to normal size (<10 mm short axis); PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions (short diameter=sum for target nodes; longest diameter=sum for all other target lesions). SD: Does not qualify for CR, PR or progression. PD: 20% increase in sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm or appearance of new unequivocal malignant lesions.

Efficacy analysis set included all enrolled participants who started the treatment of Cycle 1.

Duration of response was the time from first documentation of CR or PR to date of first documentation of PD or death for the participants with an objective response (CR or PR). Per RECIST (version 1.1). CR: complete disappearance of all target lesions except nodal disease or disappearance of all non-target lesions and normalization of tumor marker levels. All target nodes/lymph nodes must decrease to normal size (<10 mm short axis); PR: >=30% decrease under baseline of the sum of diameters of all target measurable lesions (short diameter=sum for target nodes; longest diameter=sum for all other target lesions). PD: 20% increase in sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions or appearance of new unequivocal malignant lesions. Kaplan-Meier method was used.

Efficacy analysis set included all enrolled participants who started the treatment of Cycle 1. Here, 'Overall Number of Participants Analyzed' signifies participants in the efficacy analysis set who achieved an objective response.

PFS was defined as the time from C1D1 to date of first documentation of PD or death due to any cause, whichever occurred first. Documentation of progression was by objective disease assessment as defined by the RECIST (version 1.1). PD was defined as a >=20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 millimeter (mm); or unequivocal progression of pre-existing lesions for non-target disease; or appearance of new unequivocal malignant lesions. One-year PFS probability was defined as the probability (expressed as percentage) of PFS at 1 year after C1D1. PFS probability was determined using the Kaplan-Meier method.

Efficacy analysis set included all enrolled participants who started the treatment of Cycle 1.

Plasma samples were analyzed for letrozole concentrations using a validated, sensitive and specific high-performance liquid chromatography tandem mass spectrometric (HPLC/MS/MS) method.

"Number of Participants Analyzed" represents all enrolled and treated participants who had letrozole concentration data. "Number Analyzed" represents the number of such participants who had data at each specified time point.

The pRb was one of the skin biomarkers and samples were assayed using immunohistochemistry (IHC) method. Ratio over baseline was calculated by dividing the H-score value for pRb at each specified time point by baseline value. The H-score value, which could range from 0 to 300 (strongest expression) with higher score representing stronger expression, was calculated from the total of each individual intensity of staining (0 [negative], 1+ [weak], 2+ [moderate], 3+ [strong]) multiplied by the percentages of cells (0 to 100) that represented that staining.

All enrolled and treated participants who had both pre-dose value and at least 1 post dose value for at least 1 biomarker. "Number Analyzed" refers to the number of evaluable participants for each specified time point.

The Ki67 was one of the skin biomarkers and samples were assayed using IHC method. Ratio over baseline was calculated by dividing the percentage of Ki67 positive cells at each specified time point by baseline value.

All enrolled and treated participants who had both pre-dose value and at least 1 post dose value for at least 1 biomarker. "Number Analyzed" refers to the number of evaluable participants for each specified time point.

Blood samples were collected to provide serum for the assessments of TK activity. The concentrations of TK were determined using enzyme-linked immunosorbent assay (ELISA) method. Ratio of serum TK concentration at each specified time point over baseline value was presented.

All enrolled and treated participants who had both pre-dose value and at least 1 post dose value for at least 1 biomarker. "Number Analyzed" refers to the number of evaluable participants for each specified time point.