Treatment Patterns and Clinical Outcomes Among Indian Patients Receiving Palbociclib Combinations for HR+/HER2- Advanced/Metastatic Breast Cancer in Real World Settings
Conditions: Breast Cancer, Breast Carcinoma, Breast Neoplasms, Breast Tumors, Cancer of Breast
Sponsor: Pfizer

Palbociclib  
A5481145, PD-0332991 NON-INTERVENTIONAL STUDY PROTOCOL 
Final Protocol version 1.0, 19-Oct-2020 
 
PFIZER CONFIDENTIAL 
Page 1 of 27 
 
 
Study Information 
Title  
Treatment Patterns and Clinical Outcomes Among 
Indian Patients Receiving Palbociclib Combinations 
for HR+/HER2- Advanced/Metastatic Breast Cancer 
in Real World Settings  
Protocol number  
A5481145 
Protocol version identifier  
Version 1.0  
Date   
19/10/2020 
Active substance  
L01XE33  
Palbociclib  
Medicinal product  
Palbace (palbociclib)  
Development phase 
This is a retrospective, non-interventional study 
(NIS) 
Population of interest 
Adult female patients with  
HR+/HER2- advanced/metastatic breast cancer 
Research question and objectives  
To describe patient demographics, clinical 
characteristics, treatment patterns and clinical 
outcomes of adult female patients who have received 
palbociclib combination treatments for hormone 
receptor positive/ human epidermal growth factor 2 
negative (HR+/HER2-) advanced/metastatic breast 
cancer in real world settings in India. 
Primary objectives  
• To describe demographics and clinical 
characteristics of patients who have received 

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Palbociclib  
A5481145, PD-0332991 NON-INTERVENTIONAL STUDY PROTOCOL 
Final Protocol version 1.0, 19-Oct-2020 
 
PFIZER CONFIDENTIAL 
Page 4 of 27 
1. TABLE OF CONTENTS 
2. LIST OF ABBREVIATIONS ................................................................................................5 
3. RESPONSIBLE PARTIES ....................................................................................................7 
4. ABSTRACT ...........................................................................................................................7 
5. AMENDMENTS AND UPDATES .......................................................................................9 
6. MILESTONES .......................................................................................................................9 
7. RATIONALE AND BACKGROUND ..................................................................................9 
8. RESEARCH QUESTION AND OBJECTIVES .................................................................11 
9. RESEARCH METHODS ....................................................................................................12 
9.1 Study Design ............................................................................................................12 
9.2 Setting .......................................................................................................................13 
9.2.1 Inclusion Criteria .........................................................................................13 
9.3 Variables ...................................................................................................................15 
9.4 Data Sources .............................................................................................................16 
9.5 Study Size .................................................................................................................16 
9.6 Data Management ....................................................................................................17 
9.7 Data Analysis ...........................................................................................................18 
9.8 Quality Control .........................................................................................................21 
9.9 Limitations of the Research Methods .......................................................................21 
9.10 Other Aspects .........................................................................................................22 
10. PROTECTION OF HUMAN SUBJECTS ........................................................................22 
10.1 Patient Information .................................................................................................22 
10.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ............23 
10.4 Ethical Conduct of the Study .................................................................................23 
11 MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................24 
12 PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS.........25 
13 REFERENCES ...................................................................................................................26 
 
 

Palbociclib  
A5481145, PD-0332991 NON-INTERVENTIONAL STUDY PROTOCOL 
Final Protocol version 1.0, 19-Oct-2020 
 
PFIZER CONFIDENTIAL 
Page 5 of 27 
2. LIST OF ABBREVIATIONS 
Abbreviation  
Definition  
ABC/MBC  
advanced/metastatic breast cancer  
AE  
adverse events  
AEM  
adverse events monitoring  
CDK  
cyclin-dependent kinase  
CDSCO 
Central Drugs Standard Control Organization 
DFI  
disease free interval  
eCRF  
electronic case report form 
ECOG 
Eastern Cooperative Oncology Group 
EDC 
electronic data capture 
ER 
estrogen receptor 
GPP  
Guidelines for Good Pharmacoepidemiology practices  
HER2  
human epidermal growth factor receptor 2  
HR  
hormone receptor  
HR+/HER2- 
Hormone receptor positive / human epidermal growth factor 2 
negative 
IEC  
independent ethics committee  
IRB  
institutional review board  
ISPE  
International Society for Pharmacoepidemiology  
LHRH 
Leutinizing Hormone Releasing Hormone 
NI 
non-interventional 
NIS  
non-interventional study  
ORR  
objective response rate  

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Palbociclib  
A5481145, PD-0332991 NON-INTERVENTIONAL STUDY PROTOCOL 
Final Protocol version 1.0, 19-Oct-2020 
 
PFIZER CONFIDENTIAL 
Page 8 of 27 
scarce information regarding how and when palbociclib combination is prescribed in routine 
clinical practice, and the outcomes associated with palbociclib use.  Therefore, real world 
data on the characteristics, treatment patterns and clinical outcomes among patients receiving 
palbociclib combinations to treat HR+/HER- ABC/MBC will provide valuable insight to help 
inform treatment decisions.   
Research question and objectives: The primary objective of this real world study is to 
describe the patient demographics, clinical characteristics, treatment patterns, and clinical 
outcomes of adult female patients who have received palbociclib combination treatments for 
HR+/HER2- ABC/MBC in real world settings in India.  
Study design: This retrospective physician based medical record review will collect data 
from medical records of patients, who have received palbociclib combination with aromatase 
inhibitor (as prescribed by the Physician) in menopausal state as initial endocrine therapy in 
MBC or with fulvestrant  after progression on prior endocrine therapy.  Data will be collected 
retrospectively at a single point in time from patient medical records. 
Population: Data will be collected from the Indian routine clinical practice settings. 
Approximately 10 oncologists will be included.  To be eligible to participate, physicians 
must have treated, or be treating 10 or more HR+/HER2- ABC/MBC patients with 
palbociclib combination with aromatase inhibitor (as prescribed by the Physician) in 
menopausal state as initial endocrine therapy in MBC or with fulvestrant after progression on 
prior endocrine therapy.  Each physician will complete at least 10-15 electronic case report 
forms (eCRFs).  Included physicians must go back in their records to the specific index date 
and select the next number of eligible patients for which they will complete eCRFs.  The 
‘index date’ will be defined as 60 days after the physician first prescribed palbociclib + 
partner therapy following the availability of specific indication in the market.  To be eligible, 
patients must be females, aged 18 or over, have been diagnosed with HR+/HER2- 
ABC/MBC and must have received palbociclib combination with aromatase inhibitor (as 
prescribed by the Physician) as initial endocrine therapy in postmenopausal MBC patients or 
with fulvestrant in patients who have progressed on prior endocrine therapy. For the study, 
patients must have initiated palbociclib with fulvestrant a minimum of 3 months, or 
palbociclib with aromatase inhibitor a minimum of 6 months prior to data collection.  
Variables: The variables assessed in this study will be patient demographics at the time of 
data collection, clinical characteristics, comorbid conditions, early and advanced breast 
cancer treatment history, palbociclib treatment patterns including dose changes, clinical 
outcomes and date of death if applicable.  
Data sources: Patient medical records will be used as the data source for the study.  
Study size: Approximately 10 physicians will be recruited across the India; this will enable 
data to be collected for approximately 150 patients.  
Data analysis: All analyses will be descriptive in nature.  Categorical variables will be 
described using the number of observations and number and percent (%) in each category.  

Palbociclib  
A5481145, PD-0332991 NON-INTERVENTIONAL STUDY PROTOCOL 
Final Protocol version 1.0, 19-Oct-2020 
 
PFIZER CONFIDENTIAL 
Page 9 of 27 
Numeric variables will be described using the number of observations, mean and standard 
deviation, and minimum, maximum, median and interquartile range.  Time to event will be 
described using a Kaplan-Meier chart for the median.  
Milestones: Data collection will begin in November 2020 and should be completed by  
January 2021.  Following completion of the study, the final report will be written and 
completed by February 2021. 
 
5. AMENDMENTS AND UPDATES 
NONE  
 
6. MILESTONES 
Milestone  
Planned date  
Start of data collection  
November 2020 
End of data collection  
January 2021 
Study Report 
 February 2021 
Manuscript/Conference abstract 
April 2021 
 
7. RATIONALE AND BACKGROUND  
Breast cancer is the leading cause of cancer-related death in females worldwide.  An 
approximately 1.7 million new cases of breast cancer were diagnosed in 2012, contributing to 
12% of all newly diagnosed cancers worldwide.1  According to estimates of Globocan 2012, 
India, United States and China collectively accounts for almost one third of the global breast 
cancer burden.  The reported increase in the rate of incidence and mortality due to breast 
cancer in India was 11.54% and 13.82%, respectively during 2008-2012.1  Among Indian 
females also breast cancer has been ranked the number 1 cancer with age adjusted rate as 
high as 25.8 per 100,000 women and mortality rate of 12.7 per 100,000 women.  The age 
adjusted incidence rate of carcinoma of the breast was found as high as 41 per 100,000 
women for Delhi, followed by Chennai (37.9), Bangalore (34.4) and Thiruvananthapuram 
(33.7) district.2  Breast cancer survival rates have increased over the last 50 years, as relative 
survival increased from 75.2% in 1975 to 90.6% in 2008.3  The 5-year survival rate for 
women with stage 0/I breast cancer is near to 100%, compared to that of stage II and III, 
which are 93% and 72% respectively.  Women who are diagnosed with metastatic or 
stage IV breast cancer have a much lower 5-year survival rate of 22%.4  

Palbociclib  
A5481145, PD-0332991 NON-INTERVENTIONAL STUDY PROTOCOL 
Final Protocol version 1.0, 19-Oct-2020 
 
PFIZER CONFIDENTIAL 
Page 10 of 27 
An increased understanding of breast cancer has enabled enhanced profiling of different 
disease subtypes.  Subtype classification is essential to decide on the appropriate treatment 
regime.  Breast tumors are grouped according to the expression of hormone receptors (HR) 
and human epidermal growth factor receptor 2 (HER2).  An approximately 75% of all breast 
cancer tumors are diagnosed to be HR positive (HR+) which grow in response to increased 
levels of the hormones estrogen and progesterone.  HER2 positive (HER2+) breast tumors 
grows more aggressively than HER2 negative (HER2-) tumors and represent around 15% of 
all breast tumors.5  The standardized incidence rates of HR+/HER2- breast cancer was 75.21 
per 100,000 women in 2012 across the world which accounted for 67.3% of all subtypes.6  
Over the past few decades, hormonal therapies such as letrozole and fulvestrant have 
emerged as the preferred treatment for HR+ breast cancers.  Following the success of the 
phase II PALOMA (Palbociclib: Ongoing Trials in the Management of Breast Cancer)-1 
trial, the United States Food and Drug Administration (USFDA) granted accelerated approval 
of the CDK4/CDK6 inhibitor palbociclib that causes cell cycle arrest to be used in 
combination with letrozole to treat advanced/metastatic HR+/HER2- post-menopausal breast 
cancer, making it the first CDK 4/6 inhibitor approved in breast cancer.  The PALOMA-1 
trial demonstrated median progression-free survival of 20.2 months for post-menopausal 
patients with advanced/metastatic HR+/HER- breast cancer receiving letrozole in 
combination with palbociclib vs. 10.2 months in patients receiving letrozole and placebo.7  
The follow up phase III PALOMA-2 trial demonstrated median progression free survival of 
24.8 months for post-menopausal patients with advanced/metastatic HR+/HER- breast cancer 
receiving letrozole in combination with palbociclib vs. 14.5 months in patients receiving 
letrozole and placebo.8  
In October 2016, palbociclib was granted approval to be used in combination with fulvestrant 
by the USFDA.  This was following the success of the Phase III PALOMA-3 trial, conducted 
in patients with advanced/metastatic HR+/HER- breast cancer that had relapsed or 
progressed during endocrine therapy.  The PALOMA-3 trial demonstrated a median 
progression-free survival of 9.5 months in those receiving fulvestrant in combination with 
palbociclib vs. 5.6 months in patients receiving fulvestrant with placebo.9  
Palbociclib in combination with letrozole was approved in August 2016 by the Central Drugs 
Standard Control Organization (CDSCO) for the treatment of postmenopausal women with 
estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative 
advanced breast cancer as initial endocrine- based therapy for their metastatic disease.  
Palbociclib was also granted approval to be used in combination with fulvestrant in 
December 2017 by the CDSCO for the treatment of HR+/HER2- advanced or metastatic 
breast cancer in women with disease progression following endocrine therapy.  
Palbociclib has been approved in India for over 3 years, based on the results of 3 
multinational PALOMA trials, but significant data on the clinical utility of palbociclib 
combination in routine clinical practice and outcomes associated with palbociclib use are not 
available.  Therefore, real world data on the characteristics, treatment patterns and clinical 
outcomes among patients receiving palbociclib combinations to treat HR+/HER- ABC/MBC 
will provide valuable insight to help inform treatment decisions. 

Palbociclib  
A5481145, PD-0332991 NON-INTERVENTIONAL STUDY PROTOCOL 
Final Protocol version 1.0, 19-Oct-2020 
 
PFIZER CONFIDENTIAL 
Page 11 of 27 
8. RESEARCH QUESTION AND OBJECTIVES  
The primary objective of this real-world study is to describe patient demographics, clinical 
characteristics, treatment patterns and clinical outcomes of adult female patients who have 
received palbociclib combination treatments for HR+/HER2- ABC/MBC in real world 
settings in India:  
• Palbociclib in combination with aromatase inhibitor (as prescribed by the Physician) 
for the treatment of postmenopausal women with HR+/HER2- advanced breast cancer 
as initial endocrine-based therapy for their metastatic disease.  
• Palbociclib for the treatment of hormone receptor HR+/HER2-  advanced or 
metastatic breast cancer in combination with fulvestrant in women with disease 
progression following endocrine therapy.   
Primary objectives  
• To describe the demographics and clinical characteristics of patients who have 
received palbociclib combination with aromatase inhibitor (as prescribed by the 
Physician) in menopausal state as initial endocrine therapy in MBC or with 
fulvestrant after progression on prior endocrine therapy.  
• To summarize adjuvant therapies received for the treatment of early or locally 
advanced breast cancer (Stages 0-IIIa).  
• To describe treatments received in the advanced/metastatic setting, before and after 
palbociclib combination use.  
• To describe dosing and dose changes, interruptions, delays, and discontinuations 
associated with palbociclib use in clinical practice.  
• To describe supportive therapies received by patients while receiving palbociclib 
combination treatments.  
• To determine in overall population and defined subgroups, clinical outcomes 
including (but not limited to):  
• Proportion of patients who are progression free at specific intervals (eg, 6, 12, 
18 months). 
• Objective response rate (ORR) - depending on availability of follow-up data.  
• Proportion of alive patients 1 and 2 years post palbociclib combination initiation  
- depending on availability of follow-up data (sample size permitting).  

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9.2 Setting  
Data will be collected from approximately 10 physicians recruited across India.  Each 
physician will complete at least 10-15 eCRFs.  Data will be collected retrospectively at a 
single point in time from patient medical records. 
Initial screening questions/recruitment criteria will ensure the relevant physicians are selected 
and all other non-qualifying physicians will be excluded.  In addition, during physician 
recruitment a representative geographical split and private/public practice split will be sought 
where possible to ensure a representative sample.  
To be eligible, physicians must have treated or be treating 10 or more  
HR+/HER2- ABC/MBC patients who meet the eligibility criteria for the study.  This will 
ensure that recruited physicians will be able to complete the minimum number of eCRFs 
required to participate in the study.  Once physicians have been recruited, they must go back 
to a specific index date, defined in Section 9.1 and select the next number of eligible patient 
records from patients who have been treated with a palbociclib combination.  The 
consecutive approach to recruitment will be stressed to each participating physician to limit 
selection bias.  
Each participating physician and patient must meet the following criteria to be eligible for the 
medical record reviews.  
9.2.1 Inclusion Criteria  
Physician inclusion criteria  
• Oncologist.  
• Responsible for treating ≥ 10ABC/MBC patients who meet the eligibility criteria.  
• Agrees to participate in the study and complete the eCRFs within the data collection 
period.  
Patient inclusion criteria  
Patients must meet all of the following inclusion criteria to be eligible for inclusion in the 
study: 
• ≥18 years old females. 
• HR+/HER2- breast cancer diagnosis with confirmed metastatic or advanced disease.  
• Received palbociclib with aromatase inhibitor (as prescribed by the Physician) as 
initial endocrine therapy in postmenopausal MBC patients or with fulvestrant in 
patients who have progressed on prior endocrine therapy 

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• Patients on LHRH agonists for ovarian function suppression in pre- or 
perimenopausal stage only if prescribed palbociclib with fulvestrant. 
• No prior or current enrolment in an interventional clinical trial for ABC/MBC.  
• Minimum of 3 months of follow up data since palbociclib with fulvestrant initiation, 
or minimum of 6 months of follow up data since palbociclib with aromatase inhibitor 
initiation.  
 
 
9.2.2 Exclusion criteria 
Patients meeting any of the following criteria will not be included in the study: 
• Cancers other than breast cancer 
• Male breast cancer 
• Indications other than mentioned in the protocol 
• Visceral crisis 
Overall, physicians will capture data from approximately 150 patients on demographics, 
clinical characteristics, disease history, treatment history, palbociclib dosing, clinical 
outcomes and post-palbociclib combination therapy treatment data.  The study will be 
descriptive in nature therefore no control or comparator groups will be included. 
 

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9.3 Variables  
Table 1. 
List of Study Variables 
Variable  
Role  
Data 
Source(s)  
Operational Definition  
Patient 
demographics  
Baseline  
Sub-group 
identifier  
Patient records  Age, ethnicity, weight, height, 
biomarker status, family history of 
breast cancer. 
Clinical 
characteristics  
Baseline  
Sub-group 
identifier  
Patient records  Time since diagnosis, staging, node 
status, menopause status.  
ECOG/Karnofsky functional status, 
diagnosis for which palbociclib 
combination was prescribed, sites of 
metastases, de novo vs. recurrent 
disease.  
Comorbid 
conditions  
Baseline 
Sub-group 
identifier 
Patient records  Comorbid conditions.  
Early treatment 
history  
Baseline  
Sub-group 
identifier  
Patient records  Adjuvant treatments received since 
breast cancer diagnosis, time since end 
of adjuvant treatment, 
surgery/radiotherapy received. 
Advanced 
treatment history  
Baseline  
Sub-group 
identifier  
Patient records  Treatments and supportive therapies 
received since metastatic/advanced 
HR+/HER2- diagnosis, duration of 
treatments, reasons for regimen 
changes.  
Palbociclib 
combination 
treatment  
Exposure  
Sub-group 
identifier  
Patient records  Starting dose, duration of treatment, 
line of treatment, changes in dose, 
interruptions, cycle delays and 
discontinuations; where possible 
reasons for change in treatment. 
Clinical 
outcomes  
Outcomes  
Patient records  Proportion progression free, ORR, 
TTP, PFS, patient death, 1-year and 2-
year survival in all patients and within 
specific subgroups.  

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9.4 Data Sources  
Medical records collected through routine clinical care will be used as the data source for the 
study.  
9.5 Study Size  
The study will recruit approximately 10 physicians from the routine clinical practices in India 
who will capture data from a total of approximately 150 patients. 
Table 2. 
Sample Size for Medical Record Review 
City  
Approximate Number of 
Physicians  
Number of Patient 
Records  
Mumbai 
1 
20 
Pune 
1 
10 
Delhi 
2 
40 
Bangalore 
2 
20  
Kolkata 
1 
10  
Vellore 
1 
10 
Jaipur 
1  
20 
Chennai 
1 
20 
Total (approximate):  
10  
150 
 
The sample size above (city, physician number per city, number of patient records and total 
samples) should be considered flexible, with scope to increase based on availability of 
medical records with each participating physician/site. 
The objectives do not state any hypotheses and therefore, do not require any statistical 
testing.  All the analyses will be descriptive and so sample size calculations are not required.  

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9.6 Data Management  
Physician reported data from the eCRF will be transferred to a single electronic data capture 
(EDC) tool.  All data will be de-identified and anonymized.  Incomplete data may be 
excluded from analysis following discussion with Pfizer.  Any data related queries/ 
ambiguities will be resolved in consultation with physician. 
The database will be housed in a physically and logically secure computer system maintained 
in accordance with a written security policy.  Patient confidentiality will be strictly 
maintained.  
 
9.6.1. Case report forms (CRFs)/Data collection tools (DCTs)/Electronic data record 
As used in this protocol, the term CRF 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 is required and should be completed for each included patient.  The completed 
original CRFs 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 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 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 must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs are true.  Any corrections to entries made in the CRFs or source 
documents must be dated, initialed, and explained (if necessary) and should not obscure the 
original entry. 
The source documents are the hospital or the physician's chart.  In these cases, data collected 
on the CRFs must match those charts.  
 
9.6.2. 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 patients 
(sufficient information to link records, e.g., CRFs and hospital records), all original signed 
informed consent/assent documents, copies of all CRFs, safety reporting forms, source 
documents, detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (e.g., letters, meeting minutes, and telephone call reports).  The records 

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should be retained by the investigator according to 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. 
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (e.g., 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.  
Study records must be kept for a minimum of 15 years after completion or discontinuation of 
the study, unless IQVIA and Pfizer have expressly agreed to a different period of retention 
via a separate written agreement.  Record must be retained for longer than 15 years 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. 
 
9.7 Data Analysis  
Detailed methodology for summary and statistical analyses of data collected in this study will 
be documented in a statistical analysis plan (SAP), which will be dated, filed and maintained 
by the sponsor.  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 analyses are to be descriptive and so all methods to be used will reflect this descriptive 
nature.  The specific method that will be used depends on type of variable being analyzed 
and those methods are:  
• Categorical variables – will be described using:  
• Number of observations (n);  
• Number and percent (%) within each category;  
• Number of missing observations.  
• Numeric variables – will be described using:  
• Number of observations (n);  
• Mean & Standard deviation;  
• Minimum, Maximum, Median and 1st & 3rd Quartiles;  
• Number of missing observations.  

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9.8 Quality Control  
To improve data quality the following actions will be undertaken:  
• Provision of standardized instructions on study design, methodology and procedures.  
• Physicians will be contacted via email or telephone and an overview of the study 
will be provided (detailing study objectives, patient inclusion criteria, correct 
completion of eCRF and interview and any other logistical aspects of the study). 
• Follow-up with the physicians to ensure queries are resolved quickly.  
• The electronic materials will be tested thoroughly to ensure that all questions appear 
correctly on screen, allow easy interpretation/completion and that all routing and 
logic checks are working correctly.  As such, there should be no missing data (given 
the online nature of the study, the physician will have to complete a question before 
he/she is able to move on the next) however, ‘don’t know or unknown’ will be valid 
responses.  
• To improve and secure data quality, automatic data checks upon data entry will be 
done within the eCRF.  In the eCRF, plausible ranges of values for numeric data 
entries as well as logical data entries and listings will be provided for each entry field.  
Based on this, checks on completeness and plausibility will be performed upon data 
entry in the eCRF.  All corrections will be visible from the systems audit trail. 
• No regular monitoring or source data verification is planned in this study.  However, 
in case of decreasing compliance (ie, of missing data, data discrepancies, protocol 
violations, etc.) a for-cause audit or risk-based monitoring visit will be performed. 
9.9 Limitations of the Research Methods 
A key limitation of a study of this nature is the reliance on accurate, complete eCRFs; which 
is dependent on the correct completion of the study materials and the availability of a 
detailed, complete patient records.  We have outlined several important quality control steps 
to be taken as part of the study procedures to minimize the impact of this.  Notably, to reduce 
the administrative burden on all physicians, the materials will be as short and user-friendly as 
possible.  
The representativeness of the sample is limited to the consulting population for participation, 
who has been previously prescribed palbociclib combination with aromatase inhibitor (as 
prescribed by the Physician) in menopausal state as initial endocrine therapy in MBC or with 
fulvestrant  after progression on prior endocrine therapy.  We will not collect data from 
patients from non-participating physicians, thus introducing a potential selection bias.  To 
minimize the risk of bias, multiple physicians will be recruited from a diverse geographical 
spread and mixed private/public practice where possible.  To eliminate any patient 
identification bias during data collection a systematic patient selection criterion will be 
included and stressed to each participating physician.  This will be further defined in the 

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eCRFs, but will consider the date of palbociclib approval for each indication.  Patients who 
received palbociclib prior to approval or any other indication other than mentioned in the 
protocol will not be represented in this study. 
Due to the observational design of the study, treatments received by patients may be subject 
to a channeling bias and thus must be interpreted with caution.  
9.10 Other Aspects  
Not applicable.  
10. PROTECTION OF HUMAN SUBJECTS  
10.1 Patient Information 
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 in any 
reports, publications, or 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 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 and other authorized 
parties, patient 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, patient-specific code.  
The investigator site will maintain a confidential list of patients who participated in the study, 
linking each patient’s numerical code to his or her actual identity.  In case of data transfer, 
Pfizer will maintain high standards of confidentiality and protection of patients’ personal data 
consistent with the clinical study agreement and applicable privacy laws. 
 
10.2. Patient consent 
As this study does not involve data subject to privacy laws according to applicable legal 
requirements, obtaining informed consent from patients by Pfizer is not required.   
 
 

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10.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
There must be prospective approval of the study protocol, protocol amendments, and other 
relevant documents (e.g., informed consent forms if applicable) from the relevant IRBs/IECs.  
All correspondence with the IRB/IEC must be retained.  Copies of IRB/IEC approvals must 
be forwarded to Pfizer. 
Hence, the study will be submitted to institutional review board (IRB) of respective 
participating sites for methodological review or an independent ethics committee (IEC) for 
sites with no IRB.  In addition, an IRB exemption will be sought on the basis that the study 
will collect only secondary data, no protected health information (PHI) will be collected and 
all data will be de-identified. 
 
10.4 Ethical Conduct of the Study  
The study will be conducted in accordance with legal and regulatory requirements, as well as 
with scientific purpose, value and rigor and follow generally accepted research practices 
described in Guidelines for Good Pharmacoepidemiology Practices (GPP) issued by the 
International Society for Pharmacoepidemiology (ISPE).  

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11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS  
This study protocol requires human review of patient-level unstructured data; unstructured 
data refer to verbatim medical data, including text-based descriptions and visual depictions of 
medical information, such as medical records, images of physician notes, neurological scans, 
X-rays, or narrative fields in a database.  The reviewer is obligated to report adverse events 
(AE) with explicit attribution to any Pfizer drug that appear in the reviewed information 
(defined per the patient population and study period specified in the protocol).  Explicit 
attribution is not inferred by a temporal relationship between drug administration and an AE, 
but must be based on a definite statement of causality by a healthcare provider linking drug 
administration to the AE.  
The requirements for reporting safety events on the non-interventional study (NIS) adverse 
event monitoring (AEM) Report Form to Pfizer Safety are as follows:  
• All serious and non-serious AEs with explicit attribution to any Pfizer drug that 
appear in the reviewed information must be recorded on the chart record form and 
reported, within 24 hours of awareness, to Pfizer Safety using the NIS AEM Report 
Form;  
• Scenarios involving drug exposure, including exposure during pregnancy, exposure 
during breast feeding, medication error, overdose, misuse, extravasation, lack of 
efficacy and occupational exposure associated with the use of a Pfizer product must 
be reported, within 24 hours of awareness, to Pfizer Safety using the NIS AEM 
Report Form.  
For these AEs with an explicit attribution or scenarios involving exposure to a Pfizer product, 
the safety information identified in the unstructured data reviewed is captured in the Event 
Narrative section of the report form, and constitutes all clinical information known regarding 
these AEs.  No follow-up on related AEs will be conducted. 
All the demographic fields on the NIS AEM Report Form may not necessarily be completed, 
as the form designates, since not all elements will be available due to privacy concerns with 
the use of secondary data sources.  While not all demographic fields will be completed, at the 
very least, at least one patient identifier (eg, gender, age as captured in the narrative field of 
the form) will be reported on the NIS AEM Report Form, thus allowing the report to be 
considered a valid one in accordance with pharmacovigilance legislation.  All identifiers will 
be limited to generalities, such as the statement “A 35-year-old female...” or “An elderly 
male...”  Other identifiers will have been removed.   
Additionally, the onset/start dates and stop dates for “Illness”, “Study Drug”, and “Drug 
Name” may be documented in month/year (mmm/yyyy) format rather than identifying the 
actual date of occurrence within the month/year of occurrence in the day/month/year 
(DD/MMM/YYYY) format. 

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All research staff members must complete the following Pfizer training requirements:  
• “Your reporting responsibility (YRR) Training for Vendors Working on Pfizer Studies 
(excluding interventional clinical studies and non-interventional primary data 
collection studies with sites/investigators)”.  
These trainings must be completed by research staff members prior to the start of data 
collection.  All trainings include a “Confirmation of Training Certificate” (for signature by 
the trainee) as a record of completion of the training, which must be kept in a retrievable 
format.  Copies of all signed training certificates must be provided to Pfizer.  
Re-training must be completed on an annual basis using the most current Your Reporting 
Responsibilities training materials.  
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS  
A comprehensive study report will be written on completion of study.  The reports will 
incorporate methodology, sample, analyses, tables of results and summaries.  All documents 
used throughout the study will be contained within the report as appendices.  Results of this 
study may be submitted to conferences and journals for publication.  As per Pfizer’s 
requirements, the project will only be considered complete upon delivery of the full study 
report and close of all study publications.  
In the event of any prohibition or restriction imposed (e.g., clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information which might influence the evaluation of the benefits and risks of a Pfizer 
product, Pfizer should be informed immediately.   
 

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13. REFERENCES  
1. 
Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: 
sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 
1;136(5):E359-86.  
2. 
Malvia S, Bagadi SA, Dubey US, Saxena S. Epidemiology of breast cancer in Indian 
women. Asia Pac J Clin Oncol. 2017 Aug;13(4):289-295.  
3. 
Breast cancer statistics|World Cancer Research Fund International [Internet]. [cited 
2016 Sep 23]. Available from: http://www.wcrf.org/int/cancer-facts-figures/data-
specific-cancers/breast-cancer-statistics.  
4. 
Breast cancer survival rates, by stage|American cancer society [Internet]. [Cited 2016 
Nov 30]. Available from: 
http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-survival-by-
stage.  
5. 
Dai X, Xiang L, Bai Z. Cancer Hallmarks, Biomarkers and Breast Cancer Molecular 
Subtypes. Journal of cancer. 2016;7(10):1281-1294.  
6. 
Cortet M, Bertaut A, Molinié F, et al. Trends in molecular subtypes of breast cancer: 
description of incidence rates between 2007 and 2012 from three French registries. 
BMC Cancer. 2018 Feb 7;18(1):161. 
7. 
Finn RS, Crown JP, Lang I, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib 
in combination with letrozole versus letrozole alone as first-line treatment of oestrogen 
receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a 
randomised phase 2 study. Lancet Oncol. 2015 Jan;16(1):25-35. 
8. 
Finn RS, Martin M, Rugo H, et al. Palbociclib and letrozole in advanced breast cancer. 
N Engl J Med. 2016;375:1925-1936. 
9. 
Loibl S, Turner NC, Ro J, et al. Palbociclib Combined with Fulvestrant in 
Premenopausal Women with Advanced Breast Cancer and Prior Progression on 
Endocrine Therapy: PALOMA-3 Results. Oncologist. 2017 Sep;22(9):1028-1038. 
 
 
 
 
 

Palbociclib  
A5481145, PD-0332991 NON-INTERVENTIONAL STUDY PROTOCOL 
Final Protocol version 1.0, 19-Oct-2020 
 
PFIZER CONFIDENTIAL 
Page 27 of 27 
14. LIST OF TABLES 
Table 1. 
List of Study Variables .............................................................................15 
Table 2. 
Sample Size for Medical Record Review .................................................16 
 
15. LIST OF FIGURES 
None 
 
ANNEX 1. LIST OF STAND ALONE DOCUMENTS 
None 
 
ANNEX 2. ADDITIONAL INFORMATION 
Not applicable