Prospective, Multicenter, Observational Study to Evaluate Patient-reported Outcome and Physical Activity Using Smartphone-based Application and Wearable Device in Japanese Patients With HR+/HER2- Advanced Breast Cancer Treated With Palbociclib Plus Endocrine Therapy or Endocrine Monotherapy
Phase: NA
Conditions: Breast Cancer
Sponsor: Pfizer

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This document contains confidential information belonging to Pfizer and JBCRG. Except as otherwise agreed 
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In the event of any actual or suspected breach of this obligation, Pfizer and JBCRG must be promptly notified. 
Study information 
 
Title 
Prospective, multicenter, observational study to evaluate 
patient-reported outcome and physical activity using 
smartphone-based application and wearable device in 
Japanese patients with HR+/HER2- advanced breast 
cancer treated with palbociclib plus endocrine therapy or 
endocrine monotherapy 
Study Phase 
Not applicable 
Protocol number 
A5481126 
Protocol version identifier 
Amendment 3 
Date 
20 December 2021 
Active substance 
Palbociclib (L01XE33) 
Medicinal product 
Palbociclib (IBRANCE) 
Research question and 
objectives 
The primary objectives of this prospective observational 
study are to assess change in EORTC-QLQ-C30 and 
physical activity in Japanese patients with HR+/HER2- 
advanced breast cancer receiving: 
1) Palbociclib plus endocrine therapy (Group 1) or 
2) Endocrine monotherapy (Group 2) 
Author 
PPD 
(Principal Investigator) 
Department of Breast and Endocrine Surgery, University 
of Tsukuba Hospital 
PPD 
 (Low-Interventional Study Lead) 
Medical Affairs, Pfizer Oncology Japan 
 
 

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TABLE OF CONTENTS 
1. LIST OF ABBREVIATIONS ................................................................................................ 5 
2. RESPONSIBLE PARTIES .................................................................................................... 7 
2.1. Responsible parties in JBCRG ................................................................................... 7 
2.2. Responsible parties in Pfizer ...................................................................................... 8 
3. SUMMARY ........................................................................................................................... 9 
4. AMENDMENTS AND UPDATES ....................................................................................... 9 
5. MILESTONES ..................................................................................................................... 10 
6. SCHEDULE OF ACTIVITIES ............................................................................................ 11 
7. RATIONALE AND BACKGROUND ................................................................................ 13 
8. RESEARCH QUESTION AND OBJECTIVES .................................................................. 15 
8.1. Research Objectives ................................................................................................. 15 
8.2. Research Endpoints.................................................................................................. 16 
9. RESEARCH METHODS ..................................................................................................... 17 
9.1. Study design ............................................................................................................. 17 
9.1.1. Inclusion criteria .......................................................................................... 18 
9.1.2. Exclusion criteria ........................................................................................ 19 
9.1.3. Variables ..................................................................................................... 19 
9.1.3.1. Data sources ............................................................................... 19 
10. STUDY PROCEDURES .................................................................................................... 20 
11. ASSESSMENTS ................................................................................................................ 22 
12. DATA ANALYSIS/STATISTICAL METHODS .............................................................. 23 
12.1. Study size ............................................................................................................... 23 
12.2. Data management .................................................................................................. 23 
12.3. Case Report Forms/Data Collection Tools/Electronic Data Record ...................... 24 
12.4. Record Retention ................................................................................................... 24 
12.5. Data analysis .......................................................................................................... 25 
12.5.1. Primary endpoints ..................................................................................... 25 
12.5.2. Secondary endpoints ................................................................................. 25 
CCI 
 

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12.5.4. Missing data ..............................................................................................27 
13. QUALITY CONTROL AND QUALITY ASSURANCE ..................................................27 
13.1. Site training ............................................................................................................27 
13.2. Monitoring .............................................................................................................27 
13.3. Audit ......................................................................................................................27 
13.4. Data transfers .........................................................................................................27 
13.5. Data quality assurance ...........................................................................................28 
14. LIMITATIONS OF THE RESEARCH METHODS..........................................................28 
15. PROTECTION OF HUMAN SUBJECTS .........................................................................28 
15.1. Patient Information and Consent............................................................................28 
15.2. Patient withdrawal .................................................................................................29 
15.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ..............30 
15.4. Ethical Conduct of the Study .................................................................................30 
16. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS .......................................................................................................................30 
16.1. Adverse Events (AE) .............................................................................................30 
16.2. Research-Related Injury ........................................................................................31 
16.2.1. Additional Details On Recording Adverse Events on the CRF .................33 
16.2.2. Eliciting Adverse Event Information .........................................................33 
16.2.3. Withdrawal From the Study Due to Adverse Events (see also the 
Subject Withdrawal section) .............................................................................33 
16.2.4. Time Period for Collecting AE/SAE Information .....................................33 
16.2.4.1. Reporting SAEs to Pfizer Safety ..............................................34 
16.2.4.2. Recording Non-serious AEs and SAEs on the CRF ................34 
16.2.5. Causality Assessment ................................................................................34 
16.2.6. Sponsor’s Reporting Requirements to Regulatory Authorities .................35 
16.3. Definitions .............................................................................................................35 
16.3.1. Adverse Events .........................................................................................35 
16.3.2. Abnormal Test Findings ............................................................................36 
16.3.3. Serious Adverse Events .............................................................................36 
Hospitalization ......................................................................................................37 

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16.4. Severity Assessment ..............................................................................................38 
16.5. Special Situations ...................................................................................................39 
16.5.1. Protocol-Specified Serious Adverse Events ..............................................39 
16.5.2. Exposure to the Drug under study During Pregnancy or 
Breastfeeding, and Occupational Exposure ......................................................39 
16.5.2.1. Exposure During Pregnancy ....................................................39 
16.5.2.2. Exposure During Breastfeeding ...............................................40 
16.5.2.3. Occupational Exposure ............................................................41 
16.5.3. Medication Errors......................................................................................41 
16.6. Single reference safety document ..........................................................................42 
17. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS .........42 
17.1. Reporting of Safety Issues and Serious Breaches of the Protocol .........................42 
17.2. Reporting of study results ......................................................................................42 
18. PAYMENT FOR COOPERATING THE STUDY AND COMPENSATION FOR 
RESEARCH RELATED INJURY ......................................................................................43 
18.1. Payment for study participant ................................................................................43 
18.2. Compensation ........................................................................................................43 
18.3. Burden, risk and benefit associated with study participation .................................43 
19. SPECIAL NOTES ..............................................................................................................43 
19.1. Conflict of interest .................................................................................................43 
19.2. Source of research funding ....................................................................................43 
20. REFERENCES ...................................................................................................................44 
21. LIST OF TABLES .............................................................................................................46 
22. LIST OF FIGURES ............................................................................................................46 
ANNEX 1. LIST OF STAND ALONE DOCUMENTS ..........................................................46 

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1. LIST OF ABBREVIATIONS 
 
Abbreviation 
Definition 
1L 
first line 
2L 
second line 
ABC 
advanced breast cancer 
AE 
adverse event 
BC 
breast cancer 
BYOD 
Bring Your Own Device 
CDK4/6 
cyclin-dependent kinases 4 and 6 
CI 
confidence interval 
CRF 
case report form 
CSA 
clinical study agreement 
CT 
Clinical Trial 
DCT 
data collection tool 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EDP 
exposure during pregnancy 
EORTC 
European Organisation for Research and Treatment of 
Cancer 
EORTC-QLQ-C30 
European Organisation for Research and Treatment of 
Cancer Quality of Life Questionnaire–30 (items) 
ePRO 
electronic PRO 
ER 
estrogen receptor 
ER+ 
estrogen receptor positive 
FACT-B 
Functional Assessment of Cancer Therapy – Breast 
Cancer 
HER2- 
human epidermal growth factor 2 - negative 
HR 
hormone receptor 
HR+ 
hormone receptor - positive 
HRQOL 
health-related quality of life 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
iOS 
operating system 
IRB 
Institutional Review Board 
JBCRG 
Japan Breast Cancer Research Group 
JFCR 
Japanese Foundation for Cancer Research 
J-RMP 
Japan Risk Management Plan 
MHLW 
Ministry of Health, Labour and Welfare 
MVPA 
moderate to vigorous physical activity 
PFS 
progression-free survival 
PRO 
patient reported outcome 
PRO-CTCAE 
Patient Reported Outcome - Common Terminology 
Criteria for Adverse Events 

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QOL 
quality of life 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SOP 
Standard operating procedure 
SRSD 
single-reference safety document 
TTD 
time to deterioration 
TTF 
time to treatment failure 
US-NCI 
United States - National Cancer Institute 

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2. RESPONSIBLE PARTIES 
This study will be conducted as a Pfizer-sponsored, prospective, multicenter, observational 
study, in support of Japan Breast Cancer Research Group (JBCRG), outsourced by Pfizer. 
Pfizer prepares original draft of study concept and protocol and receives scientific advices 
from Principal Investigator and the Executive Committee members assigned by JBCRG. In 
addition, the protocol will be reviewed by the JBCRG Clinical Trial Review Committee and 
JBCRG governance board in terms of academic significance, feasibility, and validity of the 
study design. 
Executive committee members in this study provide advice on the protocol synopsis, 
protocol, study conduct, and handling of operational issues from the medical and scientific 
perspectives; provide advice on site selection and data review during the study; and conduct 
interpretation of the data obtained in this study (including abstract and manuscript) and 
publication of the study data as co-authors. 
Executive committee consists of JBCRG and Pfizer, and this study will be operated by 
JBCRG and Pfizer. Site selection will be covered by JBCRG, and data management and 
monitoring will be covered by Pfizer or a third party vendor designated by Pfizer. Data 
analysis will be covered by a JBCRG and independent third party vendors designated by 
Pfizer. 
2.1. Responsible parties in JBCRG 
Research Organization 
 
Representative PPD 
of JBCRG; 
PPD 
(Department of Breast and Endocrine Surgery, Graduate school of 
Medicine, Nagoya University,) 
Executive Committee members in this study 
 
Name, degree(s) 
Affiliation 
PPD 
 MD 
(Principal Investigator) 
Department of Breast and Endocrine Surgery, University of 
Tsukuba Hospital 
PPD 
 MD 
Department of Medical Oncology, Fukushima Medical University 
PPD 
 MD 
Department of Breast and Endocrine Surgery, Tokai University 
School of Medicine 
PPD 
 
Department of Clinical Epidemiology, Translational Medical 
Center, National Center of Neurology and Psychiatry 

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PPD 
 MSc. 
Department of Clinical Trial Data Management, Tokyo University 
Graduate School of Medicine 
 
Investigators and Investigational sites 
See Appendix 1. 
2.2. Responsible parties in Pfizer 
Protocol author 
 
Name, degree(s) 
Affiliation 
PPD 
 
(Low-Interventional 
Study Lead) 
Breast cancer team, Medical Affairs, Oncology, Pfizer Japan 
 
Data center, Monitoring facility and audit facility 
See Appendix 1. 

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3. SUMMARY 
Not applicable. 
 
 
4. AMENDMENTS AND UPDATES 
Document History 
 
Document 
Version Date 
Rationale 
Original protocol 
1 June 2020 
Not applicable (N/A) 
Amendment 1 
1 September 2020 
To clarify the role and responsibility for each 
organization in this study, descriptions in Section 2 
and related sections were modified. 
As PRO data collection for "palbociclib use" was 
removed, descriptions in Section 6 and related sections 
were modified. 
Other minor edits were made. 
Amendment 2 
01 October 2021 
To update and change the research organization and 
responsible parties, description in Section 2 was 
revised. 
To clarify that the target population in this study is a 
patient who initiates first or second line endocrine- 
based treatment, descriptions in Section 8.1, Figure 1 
and 9.1.1 were revised. 
Following the revised Japanese Breast Cancer Society 
Clinical Practice Guideline, the number of patients 
who initiate endocrine monotherapy in the first or 
second-line setting has decreased thus it has become 
difficult to accumulate patients in Group 2, and the 
number of patients in Section 9.1 has been revised 
accordingly. 
Based on the comments from Independent Ethics 
Committee, descriptions were added in Section 15.1 
and Section 19.1. 
Amendment 3 
20 December 2021 
To update the planned dates of milestone based on 
actual enrollment speed, description in Section 5 and 
Section 9.1 were revised. 

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5. MILESTONES 
 
Milestone 
Planned date 
Start of data collection 
01 February 2021 
End of patient enrollment 
31 August 2022 
End of data collection 
28 February 2023 
Final study report 
31 December 2023 

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6. SCHEDULE OF ACTIVITIES 
Refer to STUDY PROCEDURES and ASSESSMENTS sections of the protocol for detailed information on each procedure and 
assessment required for compliance with the protocol. 
 
Procedure / Assessment 
Screening 
Baseline 
Observation period (6 cycles; 24 weeks)j 
End of Studyc 
Weeklya 
Cycle-baseb 
Time Window 
+ 3 daysd 
+ 7 daysd 
Informed consent 
X 
CRF data 
Patient baseline characteristics; 
Demography, Height, Weight, Medical history, 
Prior treatment and surgery history, Primary diagnosis, 
Site of metastatic and disease, Menopausal status, 
Treatment being initiated, Line of therapy 
X 
ECOG performance statusk 
X 
X→ 
X 
Adverse event monitoring (eg, type, grade)e 
X→ 
Treatment (eg, type, duration)f 
X→ 
Palbociclib dosing modificationg 
X→ 
Concomitant Medication (Surgery, Radiotherapy) 
X→ 
Disease progression (if applicable) 
X→ 
Initial treatment discontinuation (if applicable) 
X→ 
Study withdrawal (if applicable) 
X→ 
Study completion 
X 
PRO data via smartphone-based application 
Patient baseline characteristics; 
Education, Employment 
Xi 
EORTC-QLQ-C30 
Xi 
X 
PRO-CTCAEh 
Xi 
X 
Overall satisfaction with treatment 
X 

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Procedure / Assessment 
Screening 
Baseline 
Observation period (6 cycles; 24 weeks)j 
End of Studyc 
Weeklya 
Cycle-baseb 
Time Window 
+ 3 daysd 
+ 7 daysd 
Physical activity data via wearable device 
Physical activity 
X 
X→ 
 
a. 
Weekly assessment of PRO-CTCAE will be conducted based on Cycle 1 Day 1 regardless of cycle delay. 
b. Cycle-based assessment of EORTC-QLQ-C30 and Treatment satisfaction will be conducted on Day 15 of each cycle. 
c. 
End of study is defined as end of 6 cycles of initiated treatment. If patients discontinue the initiated treatment before completion of 6 cycles (eg, due to 
disease progression) and switch to another treatment, end of study will be end of 24 weeks after initiation of initial treatment. In this case, to assess 
association between change in QOL and physical activity versus disease progression, data collection [including PROs (EORTC-QLQ-C30 and PRO- 
CTCAE) and physical activity evaluation, EDC data entry] will continue to the end of the study (ie, 24 weeks after the start of the study) even if the 
treatment is switched to another treatment. 
d. Weekly-based assessments will remain open for up to 3 days (72 hours) and cycle-based assessments will remain open for up to 7 days (168 hours). 
e. 
Safety reporting will follow applicable regulations and is detailed in Section 16. 
f. 
Type and duration of treatment for advanced breast cancer used during observation period in this study (including endocrine therapy used in combination 
with palbociclib) will be collected in both group. 
g. Group 1 only. 
h. 
“Fatigue” and “General pain” are measured as PRO-CTCAE. 
i. 
Baseline assessment for PRO data will be conducted after obtaining informed consent and before initiating study treatment. 
j. 
The observation period in this study will be 6 cycles. In Group 1 (palbociclib plus endocrine therapy), palbociclib is administered for 3 consecutive weeks 
followed by 1 week off treatment to comprise 1 cycle of 4 weeks. If palbociclib is temporarily interrupted (eg, due to adverse event) and the start of the next 
cycle is delayed, the duration of one cycle may exceed 4 weeks, then, the observation period may exceed 24 weeks. In Group 2 (endocrine monotherapy), 1 
cycle is defined as 4 weeks. 
k. To be assessed at Baseline and End of study. If ECOG performance status is assessed during the observation period, the data will be entered into EDC. If 
patients discontinue the initiated treatment before completion of 6 cycles (eg, due to disease progression) and switch to another treatment, ECOG 
performance status will be assessed at end of treatment as well. 

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7. RATIONALE AND BACKGROUND 
Breast cancer is the most common cancer in women in Japan, with nearly 86,500 new cases 
diagnosed in 2018 and the incidence rate has steadily increased. In 2017, there are 14,800 
deaths as breast cancer patients. Breast cancer prevalence rate of Japanese women by age 
group began to increase from the 30s, peaked in the latter half of the 40s, after that it 
remained almost constant, and gradually decreased from the late sixties. 
Approximately 25% of women who are diagnosed with early-stage breast cancer will 
develop distant metastases. The most common subtype of advanced breast cancer is hormone 
receptor-positive, human epidermal growth factor 2-negative advanced breast cancer 
(HR+/HER2-ABC). For ER-positive breast cancer, it is relatively common to relapse after a 
long period of time, eg, 10 or more years after diagnosis. After experiencing a distant 
recurrence, patient prognosis is poor, and the overall 5-year relative survival rate is 27% for 
distant-stage disease. According to The Japanese Breast Cancer Society Clinical Practice 
Guidelines for Breast Cancer 2018, the objectives for metastatic/recurrent breast cancer are 
(1) The prolongation of survival and (2) The improvement/maintenance of the quality of life. 
Palbociclib is a selective, oral inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6) that 
prevents cell proliferation by blocking cell cycle progression from the G1 to the S phase. In 
Japan, palbociclib was approved in 2017 for the treatment of HR+/HER2- inoperable or 
recurrent breast cancer. The safety and efficacy of palbociclib were investigated in two phase 
3, randomized, double-blind, placebo-controlled, multicenter trials (PALOMA-2 and 
PALOMA-3). 
PALOMA-2 demonstrated that median progression-free survival (PFS) was 24.8 months with 
palbociclib + letrozole and 14.5 months with placebo + letrozole (hazard ratio=0.58 [95% CI, 
0.46-0.72] P<0.000001) as initial therapy for postmenopausal women with ER+/HER2- ABC. In 
Japanese subgroup analysis in PALOMA-2, median PFS was 22.2 months with palbociclib + 
letrozole vs 13.8 months with placebo + letrozole (hazard ratio=0.59 [95% CI, 0.26-1.34]). 
Common adverse events (AEs; all grades) with palbociclib + letrozole vs placebo + letrozole 
were neutropenia (81.8% vs 6.3%), infections (62.6% vs 45.0%), leukopenia (40.3% vs 
2.3%), fatigue (39.6% vs 28.4%), arthralgia (37.6% vs 36.9%), nausea (37.2% vs 27.0%), 
14.0%), alopecia (33.6% vs 16.2%), stomatitis (31.5% vs 14.9%). Grade 3/4 neutropenia 
occurred in 69.1% in patients with palbociclib + letrozole. The incidence rate of neutropenia 
with combination therapy was higher in the Japanese than in the overall population 
(neutropenia, 93.8% vs 79.5%). Grade 3/4 neutropenia occurred in 87.5% of Japanese 
patients with palbociclib + letrozole. In PALOMA-2, FACT-B was used to assess patient- 
reported outcome (PRO). There was no significant difference between palbociclib + letrozole 
and placebo + letrozole in overall change from baseline in FACT-B scores, despite the longer 
duration of treatment in the combination arm, and no significant difference in FACT-B 
HRQOL based on FACT-B total scores. The analysis of time to deterioration (TTD) in 
FACT-B showed a positive trend (hazard ratio<1) favoring the palbocilib + letrozole arm but 

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was not statistically significant (hazard ratio=0.883 [95% CI, 0.673-1.158]; one-sided 
P=0.19). 
Another phase 3 study, PALOMA-3, was conducted with HR+/HER2- patients that had 
relapsed or progressed during prior endocrine therapy. The median PFS was 9.2 months with 
palbociclib + fulvestrant and 3.8 months with placebo + fulvestrant (hazard ratio=0.42 [95% 
CI, 0.32-0.56] P<0.001). In Japanese subgroup analysis in PALOMA-3, median PFS was 
13.6 months in palbociclib + fulvestrant and 11.2 months in placebo + fulvestrant group 
(hazard ratio= 0.82 [95% CI, 0.32-2.11]). Common AEs with palbociclib + fulvestrant vs 
placebo + fulvestrant were neutropenia (84.1% vs 3.5%), leukopenia (60.0% vs 5.2%), infections 
(54.5% vs 34.9%), fatigue (44.1% vs 31.4%), Nausea (35.9% vs 30.8%), Anemia (31.6% vs 
14.0%), Stomatitis (30.1% vs 14.0%). Grade 3/4 neutropenia occurred in 69.6% of patients. 
Among Japanese patients, neutropenia was most common AE in the palbocilib arm (93%) 
and typically grade 3/4. Accordingly, dose reduction, cycle delays, and dose interruptions 
were higher in Japanese patients than in the overall populations. In PALOMA-3, EORTC- 
QLQ-C30 and EORTC-QLQ-BR23 were used to asses PRO. Analysis of PROs between the 
two treatment groups showed that estimated overall global QOL scores in EORTC-QLQ-C30 
significantly favored the palbociclib + fulvestrant (66.1, [95% CI, 64.5-67.7] versus 63.0 
[95% CI, 60.6-65.3]; P=0.0313). Significantly greater improvement from baseline in pain 
was also observed in this group (-3.3 [95% CI, -5.1 to -1.5] versus 2.0, [95% CI -0.6 to 4.6]; 
p=0.0011]). Also, TTD in global QOL and pain were significantly delayed (hazard 
ratio=0.64 [95% CI, 0.45-0.91; p<0.007, hazard ratio=0.64 [95% CI, 0.49-0.85; p<0.001, 
respectively]). 
Cancer treatment is taking place in an outpatient setting. The growing number of oral and 
subcutaneous medications for oncological diseases lead to new challenges for patients and 
health care providers. Some of the challenges include continuous patient-physician 
communication, lack of adherence, potential side effects, which are common and often 
underreported, and their impact on quality of life (QOL). One of the important purposes of 
treatment for ABC patients is to improve or maintain QOL, thus, appropriate assessment of 
patients’ QOL and the effect to daily life are important and desirable to making appropriate 
treatment decisions and assisting in timely delivery of care. 
ePRO technologies can provide a new opportunity for routine monitoring to assess patients’ 
condition, because the ability to assess PROs in real-time enables quick clinical decision- 
making and intervention. In addition, application of ePRO might enable better patient- 
clinician communication and lower symptom distress. Also, this kind of ministering provides 
a systematically collected symptom data and, thus eventually supports clinical decision- 
making to improve symptom management, which could save a lot of health care provider’s 
time, reduce the number of patients’ visits and could enhance adherence. 
Wearable devices can objectively measure physical activity. With the rapid development and 
commercialization in recent years, it has become possible to easily measure patients’ 
physical activity using wearable devices. Gresham et al.,2018 summarized 41 randomized 

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trials using wearable devices conducted on cancer patients between 2005 and 2016, 
consistent with the trend in recent years that increasing number of clinical trials have 
examined the relationship between physical activity and clinical outcomes. Some of these 
studies have suggested that the physical activity of cancer patients correlates with the 
patient's performance status, quality of life and survival. 
To date, there have been few studies in Japan evaluating the day-to-day effects of ABC 
treatment on patients in a real-world setting, and information about the effects of 
treatment-induced AEs on patients’ daily functioning outside the context of clinical trials is 
particularly lacking. This study will provide prospective, observational data in the real-world 
setting to evaluate the impact of ABC treatment and the treatment-related AEs on patients’ 
daily life utilizing novel technologies (ie, ePRO and wearable device). 
8. RESEARCH QUESTION AND OBJECTIVES 
8.1. Research Objectives 
Primary objective 
Assess change in (1) PRO as measured by EORTC-QLQ-C30 collected via smartphone- 
based application and (2) physical activity as measured by wearable device in Japanese 
patients with HR+/HER2- advanced breast cancer receiving below endocrine-based treatment 
as first or second line setting: 
1. Palbociclib plus endocrine therapy (Group 1) or 
2. Endocrine monotherapy (Group 2) 
NOTE: The study is not intended to compare outcomes between the two groups as primary 
objective. 
Secondary objectives 
The following research objectives will be addressed separately for both Group 1 and 2. 
• Assess the association between change in EORTC-QLQ-C30 and physical activity 
versus investigator-reported adverse event (AE) 
• Assess the association between change in EORTC-QLQ-C30 and physical activity 
versus patient-reported symptom as measured by PRO-CTCAE collected via 
smartphone-based application 
• Assess the association between change in EORTC-QLQ-C30 versus change in 
physical activity 

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• Assess the association between change in EORTC-QLQ-C30 and physical activity 
versus disease progression 
• Assess the feasibility of collecting physical activity data with wearable device in 
Japanese patients with advanced breast cancer 
• Assess patient’s treatment satisfaction (collected as single item via smartphone-based 
application) 
• Evaluate concordance and discordance between investigator-assessed AE versus 
PRO-CTCAE 
• Characterize patients with HR+/HER2- ABC initiating each group treatment (eg, 
baseline patient demographics and clinical characteristics) 
The following research objectives will be addressed Group 1 only. 
• Describe dosing patterns (eg, dose reduction, dose interruptions, cycle delay) 
CCI 
 
 
 
 
8.2. Research Endpoints 
Primary endpoint 
• EORTC-QLQ-C30 (Global health status scale) 
• Physical activity metrics (Sedentary time) 
Secondary endpoints 
• Other EORTC-QLQ-C30 subscales 
• Other physical activity metrics (Steps, MVPA time) 
• Adverse events and any laboratory abnormalities (Type, incidence, severity, 
seriousness and relationship to study medications) 
• PRO-CTCAE (Fatigue and General pain) 

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• Disease progression 
• Patient treatment satisfaction 
• Palbociclib treatment (including dose, dose reduction, dose interruption, cycle delay) 
9. RESEARCH METHODS 
9.1. Study design 
The study is a prospective, multicenter, observational study to evaluate PRO and physical 
activity using smartphone-based application and wearable device in Japanese patients with 
HR+/HER2- ABC. 
Patients will be enrolled into either palbociclib plus endocrine therapy group (Group 1) or 
endocrine monotherapy group (Group 2) based on the discretion of the treating physician 
under routine clinical practice. Total target number of patients is approximately one-hundred 
in this study (assuming about 20 to 80 patients in each group). The number of enrolled 
patients will be monitored, and the enrollment will be completed when 100 patients have 
been enrolled. Of note, the patient who is informed about this study for participation at the 
time when the number of enrolled patients reaches 100 is allowed to enroll.Enrolled patients 
will download a smartphone-based application for electronic PRO (ePRO), be provided 
access to and trained on the use of the application to complete baseline, weekly, and 
cycle-based assessments for 6 cycles (24 weeks). In addition, enrolled patients will be 
provided with wearable device and requested to wear the device at all-times, except of while 
bathing and sleeping, for 6 cycles (24 weeks). 
In this study, one cycle is defined as follows; 
• 
In Group 1 (palbociclib plus endocrine therapy), palbociclib is administered for 3 
consecutive weeks followed by 1 week off treatment to comprise one cycle of 4 weeks. 
If palbociclib is temporarily interrupted (eg, due to adverse event) and the start of the 
next cycle is delayed, the duration of one cycle may exceed 4 weeks, then, the 
observation period may exceed 24 weeks. 
• 
In Group 2 (endocrine monotherapy), one cycle is defined as 4 weeks. 
Participation in this study is not intended to change the routine treatment that patients receive 
as determined by their prescribing clinicians; all treatment decisions and type and timing of 
disease monitoring are at the discretion of the treating physician. No additional visits to the 
clinic will be required for the purposes of the study. 
Figure 1 summarizes the overall study design. 

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Figure 1. 
Study Design 
 
It is anticipated that all data collection for this study will occur over a 24-month period (from 
the first patient’s first visit to the last patient’s end of study assessment), 
Planned patient enrollment duration: 18 months 
Planned data collection for an individual patient: 6 cycles (24 weeks*) 
*In Group 1, if palbociclib is temporarily interrupted (eg, due to adverse event) and the start of the next 
cycle is delayed, the duration of one cycle may exceed 4 weeks, then, the observation period may exceed 
24 weeks. 
9.1.1. Inclusion criteria 
Patients diagnosed with HR+/HER2- ABC will be enrolled into this study across multiple 
centers in Japan. All patients will be required to have had a diagnosis of metastatic BC or 
advanced breast cancer not amenable to resection or radiation therapy with curative intent at 
the time of study entry. 
Patients must meet all of the following inclusion criteria to be eligible for inclusion in the 
study: 
1. Adult women (≥ 20 years of age) 
2. Diagnosis of adenocarcinoma of the breast with evidence of metastatic disease or 
advanced disease not amenable to resection or radiation therapy with curative intent. 
3. Documented evidence of HR+/HER2- tumor based on the patient’s surgical specimen or 
most recent tumor biopsy. 
4. Initiating first or second line endocrine-based treatment at study entry with one of the 
following therapies: palbociclib plus endocrine therapy or endocrine monotherapy (eg, 
letrozole, anastrozole, exemestane, fulvestrant, tamoxifen, toremifen). 
5. ECOG performance status = 0~1. 
6. Owns or has regular access to an Apple iPhone (iOS 10.0 or later) or Android phone (eg, 
Nexus or Galaxy with latest software: version 4.4 or greater). 

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7. Willing and able to complete collection of data via smartphone-based application. 
8. Willing and able to wear the wearable device for approximately 6 months. 
9. Evidence of a personally signed and dated informed consent document indicating that the 
patient has been informed of all pertinent aspects of the study. 
10. Able to read and understand Japanese. 
9.1.2. Exclusion criteria 
Patients meeting any of the following criteria will not be included in the study: 
1. The patient is participating in any interventional clinical trial that includes 
investigational or marketed products. Patients participating in other investigator- 
initiated research or non-interventional studies can be included as long as their 
standard of care is not altered by the study. 
2. The patient is on active treatment for other malignancies other than ABC. 
3. The patient’s lifestyle is fluctuating in weekly-basis (eg, shift-time worker), which 
may have high impact on physical activity assessment based to investigator’s 
discretion. 
9.1.3. Variables 
Information collected in the data collection materials will be directly transformed into 
variables; Patient baseline characteristics, treatment (type, duration, treatment modification), 
patient medical information (eg, adverse event) collected in the EDC system (eCRF); PROs 
collected in the smartphone-based application (see Schedule of Activity). EORTC-QLQ-C30 
and PRO-CTCAE will be scored according to each instrument’s scoring algorithm. Physical 
activity metrics (eg, sedentary time) will be derived by Actigraph’s algorithms based on the 
raw data collected by the device (Actigraph Insight Watch). 
Detailed definitions of additional variables that will be derived from the collected data for the 
statistical analysis will be included in the SAP. 
9.1.3.1. Data sources 
Data for this study will be obtained via the following sources: 
• Patient medical information: The investigator or designated study site staff will 
record clinical and treatment data from patients’ medical records into an eCRF 
promptly at baseline, during the observational period, and at the end of the 
observational period. Types of data to be obtained from patient medical records are 
described in Section 6 “Schedule of Activities”. 

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• Patient-Reported Outcome data: All patients will be asked to complete a baseline 
questionnaire, as well as series of questions at weekly, and cycle-based intervals via a 
smartphone-based application downloaded onto their smartphones. PRO data entered 
in smartphone-based application will be transferred into the server hosted by the 
designated PRO vendor. Two validated PRO instruments will be administered at 
baseline and weekly-basis (PRO-CTCAE) or cycle-basis (EORTC-QLQ- 
C30). Appropriate agreements with the copyright owners will be in place for use in 
this study. 
• Physical Activity data: All patients will be asked to wear a wearable device to 
record their physical activity. Physical activity raw data will be uploaded from the 
device to Actigraph CentrePoint cloud during each site visit. 
• Site characteristics information: Basic site characteristics, including geographic 
location, will be collected via Pfizer’s internal system, if applicable. 
10. STUDY PROCEDURES 
Screening and Baseline period 
Study investigators will screen patients for eligibility, obtain informed consent, and enroll 
patients meeting the eligibility criteria. Informed consent must be obtained before any study 
specific procedures are performed. Patient eligibility will be reviewed and confirmed by 
investigator or study site staff before patients are enrolled in the study. 
Investigators or study site staff will complete eCRFs to capture demographic, medical 
history, and treatment information at screening listed in Section 6 SCHEDULE OF 
ACTIVITIES. 
Enrolled patients will download a smartphone-based application for ePRO into their own 
device (ie, Bring Your Own Device [BYOD]), be provided access to and trained on the use 
of the application to complete baseline, weekly, and cycle-based assessments for 6 cycles. As 
for data to be evaluated, see “PRO data via smartphone-based application” in Section 6 
“Schedule of Activities”. Patients will complete baseline assessment for EORTC-QLQ-C30 
and PRO-CTCAE at study site, if possible. 
Investigators or study site staff will assign the wearable device to patients, and patients will 
be provided with the assigned device and be requested to wear the device at all-times, except 
of while bathing and sleeping, for 6 cycles. As baseline observation period, it is 
recommended to wear the device soon after obtaining informed consent until initiating the 
study treatment. At least 4 days is recommended for baseline observation period to obtain 
stable baseline data, but treatment schedule of each patient should be prioritized. 
Observation Period 

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The observation period in this study will be 6 cycles (24 weeks). 
In Group 1, palbociclib is administered for 3 consecutive weeks followed by 1 week off 
treatment to comprise 1 cycle of 4 weeks. If palbociclib is temporarily interrupted (eg, due to 
adverse event) and the start of the next cycle is delayed, the duration of 1 cycle may exceed 4 
weeks, then, the observation period may exceed 24 weeks. In Group 2, one cycle is defined 
as 4 weeks. 
Patients will complete PRO assessment in weekly, and cycle-basis and wear the wearable 
device for 6 cycles. At the patients’ regular clinical visits at approximately 30 day interval, 
they will bring the device worn in the past period, and study site staff will confirm if the 
returned wearable device is still functional and upload the physical activity data through 
Actigraph application (ie, ActiSync) into the Actigraph cloud system (ie, Actigraph 
CentrePoint). Detailed information will be included in User Manual and training for 
Actigraph CentrePoint for the sites. For the PRO and physical activity data collected from the 
patient, the data entry status or wearing status will be confirmed, but the data itself will not 
be confirmed. In addition, investigators or study site staff will complete eCRF to capture 
treatment changes and clinical outcomes (eg, adverse event) for 6 cycles after enrollment 
listed in SCHEDULE OF ACTIVITIES. 
If a patient has not entered any data through ePRO application for 4 consecutive weeks or if a 
patient has not worn the wearable device for 4 consecutive weeks, the study site staff will be 
notified and asked to reach out to the patient. 
Even if patients discontinue the initiated treatment before completion of 6 cycles and switch 
to another treatment, to assess association between change in QoL and physical activity 
versus disease progression, data collection (including PROs [EORTC-QLQ-C30 and PRO- 
CTCAE] and physical activity evaluation, EDC data entry) will continue to the end of the 
study (ie, 24 weeks after initiation of initial treatment). 
End of Study 
End of study is defined as end of 6 cycles of initiated treatment. If patients discontinue the 
initiated treatment before completion of 6 cycles (eg, due to disease progression) and switch 
to another treatment, end of study will be end of 24 weeks after initiation of initial treatment. 
Investigators or study site staff will complete CRF to capture End of Study information listed 
in Section 6 SCHEDULE OF ACTIVITIES. 
Patients will return the wearable device to study site staff. Study site staff will stop the 
collection of the physical activity data via configuration in Actigraph system (ie, Actigraph 
CentrePoint). Detailed information will be included in User Manual and training for 
Actigraph CentrePoint for the sites. 

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11. ASSESSMENTS 
EORTC-QLQ-C30 
The EORTC-QLQ-C30 is a 30-item questionnaire to evaluate cancer patients’ QOL, and it’s 
composed of five multi-item functional subscales (physical, role, emotional, cognitive , and 
social functioning), three multi-item symptom scales (fatigue, nausea/vomiting, and pain), a 
global quality of life (QOL) subscale, and six single item symptom scales assessing other 
cancer-related symptoms (dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, 
and the financial impact of cancer). The questionnaire employs 28 4-point Likert scales with 
responses from “not at all” to “very much” and two 7-point Likert scales for global health 
and overall QOL. Responses to all items are then converted to a 0 to 100 scale. For 
functional and global QOL scales, higher scores represent a better level of functioning/QOL. 
For symptom-oriented scales, a higher score represents more severe symptoms. A 10-point 
or higher change in scores from baseline is considered clinically significant. The linguistic 
and psychometric validation of the questionnaire into Japanese was conducted and Japanese 
translated version is available with EORTC copyright. 
One of the primary objectives of this study is to evaluate the change in PRO using 
smartphone-based application. EORTC-QLQ-C30 will be utilized in this study as PRO 
questionnaire. This instrument was chosen because EORTC-QLQ-C30 is disease-specific 
questionnaire developed for cancer patients, evaluated in clinical trials for palbociclib, and 
the items in social functioning in EORTC-QLQ-C30 can assess impacts on social activities 
and family life. 
Physical Activity Metrics 
Another primary objective of this study is to evaluate the change in physical activity using 
wearable device. Actigraph Centrepoint Insight Watch will be utilized in this study. This 
device was chosen due to a combination of factors, including metrics reported (eg, sedentary 
time, steps), validity of the device and selected metrics, availability of raw signal open to any 
valid algorithms for future processing, and >30-day battery life. 
PRO-CTCAE 
The PRO-CTCAE is a PRO measurement system that includes a library of questions that 
measure symptomatic adverse events from the patient perspective. Seventy-eight symptom 
terms that are common in oncology clinical trials can be evaluable with PRO-CTCAE, and 
each of symptom terms is assessed relative to one or more distinct attributes, including 
frequency, severity, and/or interference with usual or daily activities. Responses are provided 
on a five-point Likert scale. The linguistic and psychometric validation of the questionnaire 
into Japanese was conducted and Japanese translated version is available through US-NCI 
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Fatigue and General pain will be evaluated in this study. Fatigue is one of common adverse 
event observed in PALOMA studies, and General pain is one of the major symptoms for 
patients with ABC. Also, it is reported that these two symptoms are frequently 
underestimated, then these two are selected to evaluate in this study to understand day-to-day 
effects of ABC treatment on patients in a real-world setting. 
Treatment satisfaction 
Treatment satisfaction will be evaluated with single item question (eg, “How satisfied are 
you with your current breast cancer treatment?”). Responses are provided on a five-point 
Likert scale. Single item question is selected rather than validated questionnaire (eg, Cancer 
Therapy Satisfaction Questionnaire) considering the burden on patient regarding a number of 
questions. 
12. DATA ANALYSIS/STATISTICAL METHODS 
12.1. Study size 
The current enrollment target for this study is 100 patients across multiple centers in Japan. 
This is an observational study designed to provide descriptive summary information and is 
not designed for hypothesis testing. The number of patients was chosen on a practical basis. 
12.2. Data management 
The EDC system that will be used to capture study data at the site (eCRFs) is the Oracle 
InFORM. The EDC system will be used to collect, monitor, and report clinical data as 
specified in the protocol. Investigators or study site staff will enter clinical data into the EDC 
system at baseline, during the observational period, and at the end of study. All data 
collected via the eCRF will be reviewed by remote data managers for clarity and 
completeness. Missing or unclear data will be queried according to the data management 
plan. The database and data management plan, describing data systems used, data sources, 
data cleaning procedures, and data transfer procedures, will be generated according to 
approved specifications. 
Patient-reported outcome data will be captured using the mobile application designed, 
programmed, and hosted by PRO vendor. Physical activity data will be captured using 
Actigraph CentrePoint Insight Watch, designed, programmed, and hosted by Actigraph. 
Physical activity data will be uploaded from each patients’ device to the Actigraph 
CentrePoint cloud system during each site visit. 
Data in those systems (ie, EDC, PRO application system and Actigraph CentrePoint) will be 
reviewed by remote data managers for data entry and compliance. Patient-reported data and 
physical activity data will be transferred to clinical data management system on regular basis 
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Pfizer will extract all the data sets (ie, eCRF data, patient-reported data and physical activity 
data) and release for analysis. 
12.3. Case Report Forms/Data Collection Tools/Electronic Data Record 
As used in this protocol, the term CRF/DCT should be understood to refer to either a paper 
form or an electronic data record or both, depending on the data collection method used in 
this study. 
A CRF/DCT is required and should be completed for each included subject. The completed 
original CRFs/DCTs are the sole property of Pfizer and should not be made available in any 
form to third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer. The investigator shall ensure that the 
CRFs/DCTs are securely stored at the study site in encrypted electronic form and will be 
password protected to prevent access by unauthorized third parties. 
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety, and laboratory data entered on the CRFs/DCTs and any other data collection forms 
(source documents) and ensuring that they are accurate, authentic/original, attributable, 
complete, consistent, legible, timely (contemporaneous), enduring, and available when 
required. The CRFs/DCTs must be signed by the investigator or by an authorized staff 
member to attest that the data contained on the CRFs/DCTs are true. Any corrections to 
entries made in the CRFs/DCTs or source documents must be dated, initialed, and explained 
(if necessary) and should not obscure the original entry. 
In most cases the source documents are the hospital or the physician's chart. In these cases, 
data collected on the CRFs/DCTs must match those charts. 
In some cases, the CRF/DCT may also serve as the source document. In these cases, a 
document should be available at the investigator site, JBCRG and at Pfizer that clearly 
identifies those data that will be recorded on the CRF/DCT, and for which the CRF/DCT will 
stand as the source document. 
12.4. Record Retention 
To enable evaluations and/or inspections/audits from regulatory authorities or Pfizer, the 
investigator agrees to keep records, including the identity of all participating subjects 
(sufficient information to link records, eg, CRFs/DCTs and hospital records), all original 
signed informed consent documents, copies of all CRFs/DCTs, safety reporting forms, source 
documents, and adequate documentation of relevant correspondence (eg, letters, meeting 
minutes, and telephone call reports). The records should be retained by the investigator 
according to International Council for Harmonisation (ICH), local regulations, or as specified 
in the clinical study agreement (CSA), whichever is longer. The investigator must ensure 
that the records continue to be stored securely for so long as they are retained. 

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If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified. The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or to an independent third party arranged by Pfizer. 
Investigator records must be kept for a minimum of 5 years after completion 
completion or discontinuation of the study or for longer if required by applicable local 
regulations. 
The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met. 
12.5. Data analysis 
For the purpose of this study, analyses will generally be descriptive in nature and will be 
conducted. All analysis will be summarized separately by groups except for the between 
group comparison. Detailed methodology for summary and statistical analyses of data 
collected in this study will be documented in a SAP, which will be dated, filed and 
maintained by JBCRG and Pfizer. The SAP may modify the plans outlined in the protocol; 
any major modifications of primary endpoint definitions or their analyses would be reflected 
in a protocol amendment. 
All variables will be summarized descriptively through tabular displays of mean, median, 
ranges and standard deviations of continuous variables and frequency distributions of 
categorical variables by measured points. 
12.5.1. Primary endpoints 
• 
As primary analysis of EORTC-QLQ-C30, change in “Global health status scale” from 
baseline is summarized at each measurement time point. The mean, the 95% confidence 
interval for the mean, and the standard deviation are calculated. Baseline values are those 
measured between enrollment and the day before treatment start. 
• 
Physical activity metrics are averaged at weekly basis. As primary analysis of physical 
activity, change in “Sedentary time” from baseline is summarized at weekly basis. The 
mean, the 95% confidence interval for the mean, and the standard deviation are 
calculated. Baseline values are the average number between enrollment and the day 
before treatment start. 
12.5.2. Secondary endpoints 
Analysis of EORTC-QLQ-C30 scores 
• 
The same analysis for other 14 scales of EORTC-QLQ-C30 (5 functional scales 
[physical, role, emotional, cognitive , and social functioning], 8 symptom scales [fatigue, 
nausea/vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, and 
diarrhea], and financial difficulties scale) are performed as for global health status. 

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• 
Following analyses of 5 functional scales and Global health status scale of EORTC- 
QLQ-C30 are performed to assess the associations as follows: 
✓ Tabulate patients with and without selected investigator-reported AE at each cycle, 
summarize the mean values of change in EORTC-QLQ-C30 from baseline at each 
cycle in each tabulated population, and compare the results at Cycle 1 and Cycle 3 
using t-test 
✓ Tabulate patients with and without symptom of PRO-CTCAE at each cycle, 
summarize the mean values of change in EORTC-QLQ-C30 from baseline at each 
cycle in each tabulated population, and compare the results at Cycle 1 and Cycle 3 
using t-test 
✓ Tabulate patients with disease progression during the observation period, and 
summarize the mean values of EORTC-QLQ-C30 before and after disease 
progression 
Analysis of physical activity metrics 
• 
The same analysis for other physical activity metrics (eg, steps) is performed as for 
Sedentary time. 
• 
The similar analyses of each physical activity metrics, as same as that for EORTC-QLQ- 
C30, are performed to assess the associations. 
Association between EORTC-QLQ-C30 and Physical activity 
• 
The Pearson’s correlations between change in PRO and physical activity metrics will be 
calculated at each measurement time point. 
Patient satisfaction 
• 
Patient satisfaction will be summarized descriptively through tabular displays of mean, 
median, ranges and standard deviations of continuous variables and frequency 
distributions of categorical variables, by measured points. 
Adverse events and PRO-CTCAE 
• 
Investigator-reported AE and patient-reported AE will be summarized. 
• 
Association between investigator-reported AE and patient-reported AE will be assessed 
using contingency table and weighted Kappa coefficient. 
Feasibility of the measures 
• 
The number of responses from EORTC-QLQ-C30 and the number of physical activity 
data are summarized at each measurement point 
• 
Time from enrollment to discontinue wearing the device (ie, Time-to-wearable failure) is 
calculated, and the cumulative rate curve, median, and proportion of time-point 
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12.5.4. Missing data 
Detailed methods for handling missing data will be described in the SAP. 
 
13. QUALITY CONTROL AND QUALITY ASSURANCE 
13.1. Site training 
Investigators and study site staff will be trained with an initial on-site training session and/or 
investigator meeting on the protocol, EDC system (eCRF), smartphone-based application 
(ePRO), wearable device, documentation, and any applicable study processes. Any new 
information relevant to the performance of this study will be forwarded to the study site staff 
during the study. 
13.2. Monitoring 
This study will be investigated based on data entered in CRF whether the study is conducted 
safely and according to the protocol and data are collected accurately. In principle, 
monitoring will be centrally performed and on-site monitoring will be conducted as needed. 
13.3. Audit 
To ensure the ethics of patients participating in the study and to improve the quality of 
clinical studies, audit may be conducted to confirm whether the study is conducted in 
accordance with the ethical guidelines for medical and health research in humans, the 
Declaration of Helsinki, the protocol and standard operating procedures, etc. Auditor will 
conduct an audit at the time and frequency considered the most appropriate such as at the 
start of the study, during the study, at the end of the study, at the study data entry, data 
analysis, and the completion of clinical study report, if required. 
13.4. Data transfers 
Data transfers between Pfizer and JBCRG will be described in a detailed Data Transfer Plan. 
At the end of the study, Pfizer will transfer their complete data set to the vendor for data 
analysis, which will combine the data sets, for data analysis. Of note, transferred data may be 
used for scientific research and promotion of public health in other projects. 
CCI 

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13.5. Data quality assurance 
All applicable SOPs and data-cleaning procedures will be followed with the aim of removing 
errors and inconsistencies in the data that would otherwise affect the analysis or credibility of 
the final study report. 
14. LIMITATIONS OF THE RESEARCH METHODS 
Considering the nature of real-world observational study, the study has the potential for 
missing, inaccurate, or incomplete data. Especially, as this study require patients to 
self-report outcomes and behavior, completeness and accuracy of reporting can be a concern. 
The limitations of the observational nature can result in methodological challenges in 
attributing causality to outcomes. Hence, this study is intended for hypothesis generation as 
opposed to hypothesis confirmation. 
The patient selection and the diagnostic or monitoring procedures are those applied per the 
usual treatment paradigm of the treating physician and not dictated by the protocol. 
Heterogeneous patient populations could make the interpretation of the outcomes difficult. 
As this study will collect PRO data via smartphone-based application, participating patients 
must own and have regular access to smartphone; thus, the study population may not be 
representative of the ABC population, which may include technology- or mobile 
device-naive patients. 
As the data collection period for each patient is 6 months, feasibility of ePRO and wearable 
device (ie, ePRO data entry and wearing period) can be a concern. 
Although it is easily understood by general public, Steps is not well validated with wrist 
watches and sometimes underestimated. Therefore, Sedentary time is also evaluated to assess 
the impact of ABC treatment on patients’ physical activity. 
15. PROTECTION OF HUMAN SUBJECTS 
15.1. Patient Information and Consent 
All parties will comply with all applicable laws, including laws regarding the implementation 
of organizational and technical measures to ensure protection of patient personal data. Such 
measures will include omitting patient names or other directly identifiable data on any 
sponsor forms, reports, publications, or in any other disclosures, except where required by 
applicable laws. 
The personal data will be stored at the study site in encrypted electronic form and will be 
password protected to ensure that only authorized study staff have access. The study site 
will implement appropriate technical and organizational measures to ensure that the personal 
data can be recovered in the event of disaster. In the event of a potential personal data 

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breach, the study site shall be responsible for determining whether a personal data breach has 
in fact occurred and, if so, providing breach notifications as required by law. 
To protect the rights and freedoms of natural persons with regard to the processing of 
personal data, when study data are compiled for transfer to Pfizer, JBCRG and other 
authorized parties, subject names will be removed and will be replaced by a single, specific 
numerical code, based on a numbering system defined by Pfizer. All other identifiable data 
transferred to Pfizer or other authorized parties will be identified by this single, subject- 
specific code. The investigator site will maintain a confidential list of subjects who 
participated in the study, linking each subject’s numerical code to his or her actual identity. 
In case of data transfer, JBCRG and Pfizer will maintain high standards of confidentiality 
and protection of subject’s personal data consistent with the clinical study agreement (CSA) 
concluded among Pfizer, JBCRG and investigator site and applicable privacy laws. 
The informed consent documents must be in compliance with local regulatory requirements, 
and legal requirements, including applicable privacy laws. 
The informed consent documents used during the informed consent process must be 
reviewed and approved by Pfizer, approved by the IRB/EC before use. 
The investigator must ensure that each study subject is fully informed about the nature and 
objectives of the study, the sharing of data relating to the study and possible risks associated 
with participation, including the risks associated with the processing of the subject’s personal 
data. The investigator further must ensure that each study subject is fully informed about his 
or her right to access and correct his or her personal data and to withdraw consent for the 
processing of his or her personal data. 
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject before any study-specific activity is performed. The investigator 
will retain the original of each subject’s signed consent document. If the subject and the 
relevant person have consulted, the investigator or the study staff of each study site will 
respond. 
15.2. Patient withdrawal 
Patients may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator, in consultation with Executive 
committee of this study if needed, for safety, behavioral, or administrative reasons. In any 
circumstance, every effort should be made to document subject outcome, if applicable. The 
investigator should inquire about the reason for withdrawal and follow-up with the subject 
regarding any unresolved adverse events until the event resolve or stabilize at a level 
acceptable to the investigator. 
If the patient withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 

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collected. JBCRG and Pfizer may retain and continue to use any data collected before such 
withdrawal of consent. 
15.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents from the 
IRB/IEC. All correspondence with the IRB/IEC should be retained in the investigator file. 
Copies of IRB/IEC approvals should be forwarded to JBCRG office and Pfizer. 
The investigator must obtain IRB/IEC review and approval for the continuation of the study 
at least once a year. For annual contract renewal, the standard procedure of each institution 
shall be followed. 
The only circumstance in which an amendment may be initiated prior to IRB/IEC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects. In 
that event, the investigator must notify the IRB/IEC and Pfizer in writing immediately after 
the implementation. 
15.4. Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, legal and regulatory 
requirements, and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), ICH Guideline for Good Clinical Practice, Ethical Guidelines for 
Medical and Health Research Involving Human Subjects issued by the Ministry of Health, 
Labour and Welfare (MHLW), and the Declaration of Helsinki. 
16. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE REACTIONS 
REQUIREMENTS 
This study includes qualifying diagnostic or monitoring procedures required per protocol to 
collect clinical data needed to meet the study objectives, which are not standard-of-care but 
that do not pose more than a minimal risk or burden to the study subject. The qualifying 
procedure in this study is physical activity data collection using wearable device. 
16.1. Adverse Events (AE) 
An AE is defined as any untoward medical occurrence and can therefore be any unfavorable 
and unintended sign (including an abnormal laboratory finding), symptom, or disease, 
whether or not related to the subject’s participation in the study. 
AE reporting period for each subject begins from the time the subject provides informed 
consent, through the end of the observation period of the study which must include at least 28 
calendar days following the last administration of the drug under study. Any AE related to 

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above procedure that occurs from the time the subject consents to the clinical research 
through and including 12 hours after completion of the qualifying procedure must be 
recorded. The investigator is required to assess whether the AE may be related to the 
subject’s participation in the study. All AEs (ie, serious and non-serious, including those 
attributed to qualifying procedure identified as research-related injury) are collected in the 
clinical study database. 
The investigator must pursue and obtain information adequate to determine the outcome of 
the AE and to assess whether it meets the criteria for classification as a research-related 
injury requiring immediate notification to Pfizer as described below. 
16.2. Research-Related Injury 
Should a subject, in the investigator’s opinion, suffer a medically important research-related 
injury caused by their participation in the study, the designated Pfizer clinician or medical 
monitor must be notified immediately. 
A medically important research-related injury is any untoward medical occurrence that: 
• Results in death; 
• Is life-threatening (immediate risk of death); 
• Requires inpatient hospitalization or prolongation of existing hospitalization; 
• Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions); 
• Results in congenital anomaly/birth defect. 
Medical and scientific judgment is exercised in determining whether an injury is an 
important medical event. An important medical event may not be immediately 
life-threatening and/or result in death or hospitalization. However, if it is determined that the 
event may jeopardize the subject or may require intervention to prevent one of the other 
outcomes listed in the definition above, the important medical event should be reported as a 
research-related injury. 
An investigator may be requested by the designated Pfizer clinician or medical monitor to 
obtain specific additional follow-up information in an expedited fashion. In general, this will 
include a description of the injury in sufficient detail to allow for a complete medical 
assessment of the case and independent determination of possible causality. Information on 
other possible causes of the event, such as concomitant treatments, vaccines, and/or illnesses 
must be provided. In the case of a subject death, a summary of available autopsy findings 
must be submitted as soon as possible to Pfizer or its designated representative. 

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The table below summarizes the requirements for recording safety events on the CRF and for 
reporting safety events on the Clinical Trial (CT) Serious Adverse Event (SAE) Report 
Formto Pfizer Safety. These requirements are delineated for four types of events: (1) serious 
adverse events (SAEs); (2) non-serious AEs (as applicable); (3) scenarios involving drug 
exposure during pregnancy or breast feeding, and occupational exposure; and (4) scenarios 
involving medication errors. These events are defined in the section “Definitions of safety 
events”. Of note, treatment for advanced breast cancer administered within the observation 
period of this study (ie, palbociclib plus endocrine therapy or endocrine monotherapy) is 
described as "drug under study". 
 
Safety event 
Recorded on the CRF 
Reported on the CT SAE 
Report Form to Pfizer 
Safety within 24 hours of 
awareness 
SAE 
All 
All 
Non-serious AE 
All 
None 
Scenarios involving exposure 
to a drug under study, 
including exposure during 
pregnancy, exposure during 
breast feeding, and 
occupational exposure 
All (regardless of whether 
associated with an AE), 
except occupational 
exposure 
All (regardless of whether 
associated with an AE) 
Note: Any serious 
associated adverse event is 
reported together with the 
exposure scenario. 
For occupational exposure, 
both serious and non-serious 
AEs are reported 
 
Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report 
Form within 24 hours of awareness of the event by the investigator are to be reported 
regardless of whether the event is determined by the investigator to be related to the drug 
under study. In particular, if the SAE is fatal or life-threatening, notification to Pfizer Safety 
must be made immediately, irrespective of the extent of available event information. This 
time frame also applies to additional new (follow-up) information on previously forwarded 
reports. In the rare situation that the investigator does not become immediately aware of the 
occurrence of an event, the investigator must report the event within 24 hours after learning 
of it and document the time of his/her first awareness of the event. 
For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see the Serious Adverse Events section below). In addition, the investigator may be 
requested by Pfizer Safety to obtain specific follow-up information in an expedited fashion. 
This information is more detailed than that recorded on the CRF. In general, this will include 

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a description of the event in sufficient detail to allow for a complete medical assessment of 
the case and independent determination of possible causality. Any information relevant to 
the event, such as concomitant medications and illnesses, must be provided. In the case of a 
subject death, a summary of available autopsy findings must be submitted as soon as possible 
to Pfizer Safety. Any pertinent additional information must be reported on the CT SAE 
Report Form; additional source documents (eg, medical records, CRF, laboratory data) are to 
be sent to Pfizer Safety ONLY upon request. 
As part of ongoing safety reviews conducted by the sponsor, any non-serious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE. To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical 
study. 
16.2.1. Additional Details On Recording Adverse Events on the CRF 
All events detailed in the table above will be recorded on the AE page(s) of the CRF. It 
should be noted that the CT SAE Report Form for reporting of SAE information is not the 
same as the AE page of the CRF. When the same data are collected, the forms must be 
completed in a consistent manner. AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE Report 
Form for reporting of SAE information. 
16.2.2. Eliciting Adverse Event Information 
The investigator is to record on the CRF all directly observed AEs and all AEs spontaneously 
reported by the study subject. In addition, each study subject will be questioned about the 
occurrence of AEs in a non-leading manner. 
16.2.3. Withdrawal From the Study Due to Adverse Events (see also the Subject Withdrawal 
section) 
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted below, and recorded on the CRF. 
When a subject withdraws from the study because of an SAE, the SAE must be recorded on 
the CRF and reported, as appropriate, on the CT SAE Report Form, in accordance with the 
Requirements section above. 
16.2.4. Time Period for Collecting AE/SAE Information 
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each subject begins from the time the subject provides informed consent, which 
is obtained before the subject’s participation in the study (ie, before undergoing any study- 
related procedure and/or receiving the marketed product under study), through the end of the 

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observation period of the study which must include at least 28 calendar days following the 
last administration of the drug under study. 
For subjects who are screen failures, the active collection period ends when screen failure 
status is determined. 
16.2.4.1. Reporting SAEs to Pfizer Safety 
All SAEs occurring in a subject during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form. 
SAEs occurring in a subject after the active collection period has ended are reported to Pfizer 
Safety if the investigator becomes aware of them; at a minimum, all SAEs that the 
investigator believes have at least a reasonable possibility of being related to drug under 
study must be reported to Pfizer Safety. 
Follow up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and 
Pfizer concurs with that assessment. 
If a patient begins a new anticancer therapy, SAEs occurring during the above-indicated 
active collection period must still be reported to Pfizer Safety irrespective of any intervening 
treatment. 
16.2.4.2. Recording Non-serious AEs and SAEs on the CRF 
During the active collection period, both non-serious AEs and SAEs are recorded on the 
CRF. 
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment. 
If a patient begins a new anticancer therapy, the recording period for non-serious AEs ends at 
the time the new treatment is started; however, SAEs and research-related injury due to 
wearable device must continue to be recorded on the CRF during the above-indicated active 
collection period. 
16.2.5. Causality Assessment 
The investigator’s assessment of causality must be provided for all AEs (serious and non- 
serious); the investigator must record the causal relationship on the CRF, and report such an 
assessment in accordance with the SAE reporting requirements, if applicable. An 
investigator’s causality assessment is the determination of whether there exists a reasonable 
possibility that the drug under study caused or contributed to an AE; generally the facts 
(evidence) or arguments to suggest a causal relationship should be provided. If the 
investigator does not know whether or not the drug under study caused the event, then the 

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event will be handled as “related to drug under study” for reporting purposes, as defined by 
the sponsor. If the investigator's causality assessment is “unknown but not related” to drug 
under study, this should be clearly documented on study records. 
In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, and 
report such an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements. 
16.2.6. Sponsor’s Reporting Requirements to Regulatory Authorities 
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations. 
16.3. Definitions 
16.3.1. Adverse Events 
An AE is any untoward medical occurrence in a study subject administered a product or 
medical device; the event need not necessarily have a causal relationship with the treatment 
or usage. Examples of AEs include, but are not limited to: 
• Abnormal test findings; 
• Clinically significant signs and symptoms; 
• Changes in physical examination findings; 
• Hypersensitivity; 
• Drug abuse; 
• Drug dependency. 
• Additionally, AEs may include signs and symptoms resulting from: 
• Drug overdose; 
• Drug withdrawal; 
• Drug misuse; 
• Drug interactions; 
• Extravasation; 

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• Exposure during pregnancy (EDP); 
• Exposure via breastfeeding; 
• Medication error; 
• Occupational exposure. 
Worsening of signs and symptoms of the malignancy under study should be recorded as AEs 
in the appropriate section of the CRF. Disease progression assessed by measurement of 
malignant lesions on radiographs or other methods should not be reported as AEs. 
16.3.2. Abnormal Test Findings 
Abnormal objective test findings should be recorded as AEs when any of the following 
conditions are met: 
• Test result is associated with accompanying symptoms; and/or 
• Test result requires additional diagnostic testing or medical/surgical intervention; and/or 
• Test result leads to a change in study dosing or discontinuation from the study, significant 
additional concomitant drug treatment, or other therapy; and/or 
• Test result is considered to be an AE by the investigator or sponsor. 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE. Any abnormal test result that is determined to be an error does not require 
recording as an AE. 
16.3.3. Serious Adverse Events 
A serious adverse event is any untoward medical occurrence at any dose that: 
• Results in death; 
• Is life-threatening (immediate risk of death); 
• Requires inpatient hospitalization or prolongation of existing hospitalization; 
• Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions); 
• Results in congenital anomaly/birth defect. 
Or that is considered to be: 

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• An important medical event. 
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event. An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization. However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious. 
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse. 
Progression of the malignancy under study (including signs and symptoms of progression) 
should not be reported as an SAE unless the outcome is fatal within the active collection 
period. Hospitalization due to signs and symptoms of disease progression should not be 
reported as an SAE. If the malignancy has a fatal outcome during the study or within the 
active collection period, then the event leading to death must be recorded as an AE on the 
CRF, and as an SAE with Common Terminology Criteria for Adverse Events (CTCAE) 
Grade 5 (see the Severity Assessment section). 
16.3.4. Hospitalization 
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility, or any prolongation of an existing admission. Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit). An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit is assessed for medical importance. 
Hospitalization does not include the following: 
• Rehabilitation facilities; 
• Hospice facilities; 
• Respite care (eg, caregiver relief); 
• Skilled nursing facilities; 
• Nursing homes; 
• Same-day surgeries (as outpatient/same-day/ambulatory procedures). 
• Hospitalization or prolongation of hospitalization in the absence of a precipitating clinical 
AE is not in itself an SAE. Examples include: 

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• Admission for treatment of a preexisting condition not associated with the development 
of a new AE or with a worsening of the preexisting condition (eg, for workup of a 
persistent pretreatment laboratory abnormality); 
• Social admission (eg, subject has no place to sleep); 
• Administrative admission (eg, for yearly physical examination); 
• Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol); 
• Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery); 
• Hospitalization for observation without a medical AE; 
• Preplanned treatments or surgical procedures. These should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject; 
• Admission exclusively for the administration of blood products. 
Diagnostic and therapeutic noninvasive and invasive procedures, such as surgery, should not 
be reported as SAEs. However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an SAE. For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the 
AE. 
16.4. Severity Assessment 
 
GRADE Clinical Description of Severity 
0 
No change from normal or reference range (This grade is not included in the 
Version 4.03 CTCAE document but may be used in certain circumstances.) 
1 
MILD adverse event 
2 
MODERATE adverse event 
3 
SEVERE adverse event 
4 
LIFE-THREATENING consequences; urgent intervention indicated 
5 
DEATH RELATED TO adverse event 
 
Note the distinction between the severity and the seriousness of an AE. A severe event is not 
necessarily an SAE. For example, a headache may be severe (interferes significantly with 

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the subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above. 
16.5. Special Situations 
16.5.1. Protocol-Specified Serious Adverse Events 
There are no protocol-specified SAEs in this study. All SAEs will be reported to Pfizer 
Safety by the investigator as described in previous sections, and will be handled as SAEs in 
the safety database. 
16.5.2. Exposure to the Drug under study During Pregnancy or Breastfeeding, and Occupational 
Exposure 
Exposure to the drug under study under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness. 
16.5.2.1. Exposure During Pregnancy 
For marketed products, an exposure during pregnancy (EDP) occurs if: 
1. A female becomes, or is found to be, pregnant either while receiving or having been 
exposed (eg, because of treatment or environmental exposure) to the drug under 
study; or the female becomes or is found to be pregnant after discontinuing and/or 
being exposed to the drug under study; 
o An example of environmental exposure would be a case involving direct 
contact with a Pfizer product in a pregnant woman (eg, a nurse reports that she 
is pregnant and has been exposed to chemotherapeutic products). 
2. A male has been exposed (eg, because of treatment or environmental exposure) to the 
drug under study prior to or around the time of conception and/or is exposed during 
his partner’s pregnancy. 
If a subject or subject’s partner becomes or is found to be pregnant during the subject’s 
treatment with the drug under study, the investigator must report this information to Pfizer 
Safety on the CT SAE Report Form and an EDP supplemental form, regardless of whether an 
SAE has occurred. In addition, the investigator must submit information regarding 
environmental exposure to a Pfizer product in a pregnant woman (eg, a subject reports that 
she is pregnant and has been exposed to a cytotoxic product by inhalation or spillage) to 
Pfizer Safety using the EDP supplemental form. This must be done irrespective of whether 
an AE has occurred and within 24 hours of awareness of the exposure. The information 
submitted should include the anticipated date of delivery (see below for information related 
to termination of pregnancy). 

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Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome. The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety of the outcome as a 
follow-up to the initial EDP supplemental form. In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth. In the event of a termination, the 
reason(s) for termination should be specified and, if clinically possible, the structural 
integrity of the terminated fetus should be assessed by gross visual inspection (unless pre- 
procedure test findings are conclusive for a congenital anomaly and the findings are 
reported). 
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live-born baby, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs. 
Additional information about pregnancy outcomes that are reported to Pfizer Safety as SAEs 
follows: 
• Spontaneous abortion includes miscarriage and missed abortion; 
• Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs. In addition, infant deaths after 1 month should be reported as SAEs 
when the investigator assesses the infant death as related or possibly related to exposure 
to the drug under study. 
Additional information regarding the EDP may be requested by the sponsor. Further follow- 
up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on preterm 
infants to identify developmental delays). In the case of paternal exposure, the investigator 
will provide the subject with the Pregnant Partner Release of Information Form to deliver to 
his partner. The investigator must document in the source documents that the subject was 
given the Pregnant Partner Release of Information Form to provide to his partner. 
16.5.2.2. Exposure During Breastfeeding 
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form. An exposure during breastfeeding report is not created when a Pfizer 
drug specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use. However, if the infant experiences an SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding. 

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16.5.2.3. Occupational Exposure 
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE. 
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated 
SAE. 
When the occupational exposure is associated with an adverse event, it is reported to Safety 
regardless of the seriousness criterion associated with that adverse event. 
Since the information does not pertain to a subject enrolled in the study, the information is 
not recorded on a CRF; however, a copy of the completed CT SAE Report Form is 
maintained in the investigator site file. 
16.5.3. Medication Errors 
Other exposures to the drug under study may occur in studies, such as medication errors. 
 
Safety Event 
Recorded on the CRF 
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness 
Medication errors 
All (regardless of whether 
associated with an AE) 
Only if associated with an 
SAE 
 
Medication errors may result from the administration or consumption of the drug under study 
by the wrong subject, or at the wrong time, or at the wrong dosage strength. 
Medication errors include: 
• Medication errors involving subject exposure to the drug under study; 
• Potential medication errors or uses outside of what is foreseen in the protocol that do or 
do not involve the participating subject. 
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page. 
In the event of a medication dosing error, the sponsor should be notified immediately. 
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 

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applicable, any associated AE(s), serious and non-serious, are recorded on an AE page of the 
CRF. 
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE. 
16.6. Single reference safety document 
The Japan package insert for drug under study including palbociclib will serve as the single 
reference safety document during the course of the study, which will be used by Pfizer safety 
to assess any safety events reported to Pfizer Safety by the investigator during the course of 
this study. 
The SRSD should be used by the investigator for prescribing purposes and guidance. 
17. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS 
17.1. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP 
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the drug under 
study, Pfizer should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of. 
17.2. Publications by Investigators 
Study results will be presented at appropriate scientific meetings and reported as papers. 
Caution will be exercised in protecting the confidentiality of personal information when 
making presentations. After the publication of the primary results, study site may use the 
study results obtained from each study sites. However, if information on the present research 
(including the introduction of the study and case report, etc.) is presented externally, the 
purpose and content of the presentation (including the date, time, place, title, presenter, and 
abstract, etc.) should be notified to Executive committee of this study and the approval 
should be obtained before the submission. Any patent or other intellectual property rights 
arising from the results of this study are determined by JBCRG and Pfizer after discussion. 
This study will be registered in the ClinicalTrials.gov, etc. and the information will be 
disclosed. The registration shall be performed by the principal investigator, JBCRG office 
and/or Pfizer. 

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18. PAYMENT FOR COOPERATING THE STUDY AND COMPENSATION FOR RESEARCH 
RELATED INJURY 
18.1. Payment for study participant 
The contents of medical care in this study are similar to those in usual medical care. The 
treatment in this study is performed at the range of daily medical care using drugs already 
approved. Therefore, all medical expenses including drugs and investigations during the 
study period will be covered by public health insurance and the patient’s own copayment. In 
order to reduce the burden on participation in this study, patients will be paid 20,000 yen or 
an equivalent amount of gift voucher for study participation upon completion or 
discontinuation of the study. 
18.2. Compensation 
If an adverse event occurs during the study, the investigator will promptly take necessary 
measures (investigation, treatment, and study discontinuation) to ensure the safety of the 
study participants. In such case, the best medical care within the range of public health 
insurance treatment shall be provided. Compensation will be made for injury associated with 
the procedures required for participation in this study (ie, wearing of wearable device). 
However, compensation will not be made for other injury. Investigator shall take necessary 
measures such as insurance for indemnification before the start of this study in preparation 
for liability. 
18.3. Burden, risk and benefit associated with study participation 
All drugs used in this study have been approved for the indication, and all treatments will be 
covered by public health insurance. All medical expenses including drug expenses during the 
study will be covered by public health insurance and the patient’s own copayment. 
Therefore, there is no economic benefit to patients from taking part in this study compared to 
routine clinical practice (excluding the above-mentioned payment for study participants). 
Disadvantages include the occurrence of adverse events observed in clinical studies 
conducted to date, and in some cases, treatment-related death. However, this can also happen 
in routine clinical practice, and it does not change because of participation in the present 
research. 
19. SPECIAL NOTES 
19.1. Conflict of interest 
Any potential conflicts of interest in the planning, conduct, and publication of this study will 
be disclosed. Conflict of interest refers to an interest that may affect study results, including 
financial and personal relationships. Since this study is a multicenter study, each 
investigator's conflicts of interest are managed by each study site. 
19.2. Source of research funding 
This study will be conducted with Pfizer funding. 

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20. REFERENCES 
1. Center for Cancer Control and Information Services, National Cancer Center; 
https://ganjoho.jp/en/public/statistics/short_pred.html 
2. The Japanese Breast Cancer Society. Clinical Practice Guidelines for Breast Cancer 
2018; http://jbcs.gr.jp/guidline/2018/ 
3. Schairer C, Mink PJ, Carroll L, et al. Probabilities of death from breast cancer and other 
causes among female breast cancer patients. J Natl Cancer Inst. 2004;96(17):1311-21. 
4. American Cancer Society. Breast cancer facts & figures 2017–2018. American Cancer 
Society. 2017. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and- 
statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2017-2018.pdf 
5. Pan H, Gray R, Braybrooke J, et al. 20-Year Risks of Breast-Cancer Recurrence after 
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12. Turner NC, Ro J, André F, et al. Palbociclib in Hormone-Receptor-Positive Advanced 
Breast Cancer. N Engl J Med. 2015;373(3):209-19. 

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13. Masuda N, Inoue K, Nakamura R, et al. Palbociclib in combination with fulvestrant in 
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25. Xie J, Wen D, Liang L, et al. Evaluating the Validity of Current Mainstream Wearable 
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30. Miyaji T, Iioka Y, Kuroda Y, et al. Japanese translation and linguistic validation of the 
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Terminology Criteria for Adverse Events (PRO-CTCAE). J Patient Rep Outcomes. 
2017;1(1):8. 
31. Kawaguchi T, Azuma K, Sano M, et al. The Japanese version of the National Cancer 
Institute's patient-reported outcomes version of the common terminology criteria for 
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21. LIST OF TABLES 
None 
22. LIST OF FIGURES 
Figure 1. Study Design 
23. ANNEX 1. LIST OF STAND ALONE DOCUMENTS 
Appendix 1. Contact details of responsible parties and all investigators 
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