Treatment Patterns and Clinical Outcomes Among Talazoparib-Treated Adults With HER2-Negative Metastatic Breast Cancer and Germline BRCA1/2 Mutations: An Observational Study Using Flatiron Electronic Health Record (EHR) Database
Conditions: Metastatic Breast Cancer, Breast Neoplasms
Sponsor: Pfizer

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NON-INTERVENTIONAL (NI) STUDY PROTOCOL
Study information
Title
Treatment Patterns and Clinical Outcomes Among 
Talazoparib-Treated Adults with HER2-Negative
Metastatic Breast Cancer and Germline BRCA1/2
Mutations:  An Observational Study Using Flatiron 
Electronic Health Record (EHR) Database 
Protocol number
C3441055
Protocol version identifier
1.0
Date
16 November 2021
Active substance
Talazoparib
Medicinal product
TALZENNA®
Research question and 
objectives
Objectives: 
The following objectives will be assessed descriptively 
among adult patients with human epidermal growth 
factor receptor 2 (HER2)-negative metastatic breast 
cancer (mBC) with germline breast cancer susceptibility 
gene 1 or 2 (gBRCA1/2) mutations treated with 
talazoparib in first-line or later line of therapy in the real-
world (RW) practice setting in the United States (US):
Primary objective
•
Describe time to treatment failure (TTF) with 
talazoparib for talazoparib-treated patients
 
 
 
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Authors
 MA (Principal Investigator)
Health Economics and Outcomes Research 
(Oncology)
Pfizer, Inc
Email:
Phone:
PharmD, RPh, MPH 
Global Health Economics and Outcomes 
Research (Oncology)
Pfizer, Inc
Email: 
Phone:
This document contains confidential information belonging to Pfizer.  Except as otherwise agreed to in 
writing, by accepting or reviewing this document, you agree to hold this information in confidence and not 
copy or disclose it to others (except where required by applicable law) or use it for unauthorized purposes.  In 
the event of any actual or suspected breach of this obligation, Pfizer must be promptly notified.
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1. TABLE OF CONTENTS
1. TABLE OF CONTENTS.......................................................................................................3
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 ....................................................................................................11
9.1. Study design ............................................................................................................11
9.2. Setting......................................................................................................................12
9.2.1. Inclusion criteria .........................................................................................12
9.2.2. Exclusion criteria........................................................................................13
9.3. Variables..................................................................................................................13
9.4. Data sources ............................................................................................................19
9.5. Study size ................................................................................................................20
9.6. Data management....................................................................................................20
9.7. Data analysis ...........................................................................................................20
9.8. Analysis overview...................................................................................................20
9.8.1. Analysis of baseline characteristics............................................................21
9.8.2. Analysis of clinical outcomes.....................................................................21
9.9. Quality control.........................................................................................................23
9.10. Limitations of the research methods .....................................................................23
9.11. Other aspects .........................................................................................................23
10. PROTECTION OF HUMAN SUBJECTS ........................................................................23
10.1. Patient information................................................................................................23
10.2. Patient consent.......................................................................................................24
10.3. Institutional review board (IRB)/Independent ethics committee (IEC)................24
10.4. Ethical conduct of the study..................................................................................24
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11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................25
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........25
13. REFERENCES ..................................................................................................................26
14. LIST OF TABLES.............................................................................................................27
15. LIST OF FIGURES ...........................................................................................................31
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS.........................................................31
ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS .........................................31
ANNEX 3. ADDITIONAL INFORMATION.........................................................................31

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2. LIST OF ABBREVIATIONS
Abbreviation
Definition
ABC
advanced breast cancer
AE
adverse event
AIDS
acquired immunodeficiency syndrome
ATU
Autorisation Temporaire d'Utilisation (temporary 
authorization for use)
BC
breast cancer
BRCA1
Breast cancer susceptibility gene 1
BRCA2
Breast cancer susceptibility gene 2
CDK 
cyclin-dependent kinase 
CI
confidence interval
ECOG
Eastern Cooperative Oncology Group performance status
EHR
Electronic Health Record
ER
estrogen receptor
FDA
Food and Drug Administration
gBRCA1/2
germline BRCA1 or 2 
GPP
Good Pharmacoepidemiology Practices
HER2
human epidermal growth factor receptor 2
HIV
human immunodeficiency virus
HR
hormone receptor
IEC
Independent Ethics Committee
IQR
interquartile range
IRB
Institutional Review Board

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Abbreviation
Definition
ISPE
International Society for Pharmacoepidemiology
KM
Kaplan-Meier
mBC
metastatic breast cancer
OR
odds ratio
PARP
Poly(adenosine diphosphate–ribose) polymerase
PDF
portable document format
PD-L1
Programmed death ligand 1
PFS
progression-free survival
PgR
progesterone receptor
PH
proportional hazards
PHI
Protected Health Information
QC
quality control
RW
real-world
SSDI
Social Security Death Index
STD
standard deviation
STROBE
Strengthening the Reporting of Observational Studies in 
Epidemiology
TNBC
triple-negative breast cancer
TTF
time to treatment failure
US
United States
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3. RESPONSIBLE PARTIES
Principal Investigator(s) of the Protocol
Name, degree(s)
Job Title
Affiliation
Address
MA
Health Economics and 
Outcomes Research 
(Oncology)
Pfizer, Inc.
219 East 42nd 
Street New York, 
NY 10017
PharmD, RPh, 
MPH
Global Health 
Economics and 
Outcomes Research 
(Oncology)
Pfizer, Inc.
219 East 42nd 
Street New York, 
NY 10017
4. ABSTRACT
Treatment Patterns, and Clinical Outcomes Among Talazoparib-Treated Adults with HER2-
Negative Metastatic Breast and Germline BRCA1/2 Mutations:  An Observational Study 
Using Flatiron Electronic Health Record (EHR) database
Version 1, 16 November 2021
Main author:
PharmD, RPh, MPH
Global Health Economics and Outcomes Research (Oncology)
Rationale and background
Talazoparib (TALZENNA®) is an orally available poly (adenosine diphosphate–ribose) 
polymerase (PARP) inhibitor indicated for treatment of adult patients with human epidermal
growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC, including locally 
advanced or metastatic breast cancer) and germline breast cancer susceptibility gene 1 or 2 
(gBRCA1/2) mutations. To date, the only information available about the real-world 
experience with talazoparib, including patient characteristics, treatment patterns, and clinical 
outcomes comes from compassionate use programs in Turkey, and Russia, and the French 
temporary authorization for use (ATU) program.  Since the approval of talazoparib in the 
United States (US) in 2018, there is no published data about the real-world (RW) experience 
of talazoparib-treated patients with HER2-negative ABC with gBRCA1/2 mutations in the 
US.     
Research question and objectives
The following objectives will be assessed descriptively among adult patients with HER2-
negative metastatic breast cancer (mBC) with gBRCA1/2 mutations treated with talazoparib 
in first-line or later line of therapy in the RW practice setting in the US.
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Primary objective
•
Describe time to treatment failure (TTF) with talazoparib for talazoparib-treated patients
 
Study design
This is an observational study using de-identified EHR data from Flatiron Health Analytic 
Database.  
Population
The study population includes adult patients with HER2-negative mBC with gBRCA1/2
mutations who initiated talazoparib in first or later line of therapy identified from the Flatiron 
Health Analytic Database. 
 
 
Data sources
EHR data from Flatiron Health Analytic Database. 
Study size
Approximately 40 patients with gBRCA1/2 mutated HER2- mBC who have received 
treatment with talazoparib.  
Data analysis
 For time-to-event analyses endpoints such as TTF,
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 the Kaplan-Meier 
(KM) method will be used, accounting for right-censoring. 
 
 
 
 
 
 
 
 
 
 
5. AMENDMENTS AND UPDATES
None.
6. MILESTONES
Milestone
Planned date
Tables for Abstract Submission to 2022 Miami Breast, ASCO 2022, 
ESMO BC 
31 December 2021
Start of data collection 
22 November 2021
End of data collection
31 December 2021
Final tables
28 February 2022
Final study report
31 March 2022 
7. RATIONALE AND BACKGROUND
Breast cancer (BC) represents a major public health problem, with 284,200 new cases and 
44,130 deaths estimated in the United States (US) during 2021.1 Prognosis with metastatic 
BC (mBC) is poor, with an estimated 5-year survival rate of approximately 28.1%.2 Although 
the advent of novel therapeutic interventions such as immunotherapy and targeted agents 
have brought major strides in the treatment of advanced breast cancer (ABC, including 
locally advanced or metastatic breast cancer), patients may continue to experience minimal
or short-lived responses to these agents.2 As such, the development and characterization of 
effective interventions are greatly needed in order to ensure patient-specific, appropriate, and 
tolerable treatment that achieves meaningful improvement in survival and quality of life. By 
increasing understanding of the true efficacy, safety, effectiveness, and treatment patterns of 
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ABC-focused regimens in a broad, real-world (RW) patient population, RW studies can add 
tremendous value to this process.3
BC is classified into 4 main disease subtypes based on hormone receptor (HR) status (i.e., 
estrogen receptor (ER) and progesterone receptor (PgR) and human epidermal growth factor 
receptor 2 (HER2) expression, including HR-positive/HER2-negative (luminal A), HR-
negative/HER2-negative (triple-negative breast cancer [TNBC]), HR-positive/HER2-positive 
(luminal B), and HR-negative/HER2-positive (HER2-enriched).4 Each subtype is associated 
with distinct disease features as well as treatment recommendations.4,5 Treatment strategy 
may also be driven by mutation status of certain genes, including the BC susceptibility gene 
1 or 2 (BRCA1 or BRCA2), in which mutations may render cells deficient in the repair of 
DNA double-strand breaks, thereby increasing reliance on poly(adenosine diphosphate–
ribose) polymerase (PARP)-dependent, single-strand break repair mechanisms.5-8 Germline 
BRCA1 or BRCA2 (gBRCA1/2) mutations account for approximately 5% of all BC cases, 
with prevalence of these mutations higher among those with HER2-negative disease.9-11
Talazoparib (TALZENNA®), which was approved by the US Food and Drug Administration 
(FDA) on October 16, 2018, is an orally available PARP inhibitor indicated for treatment of 
adult patients with HER2-negative ABC (including locally advanced or metastatic breast 
cancer) and germline breast cancer susceptibility gBRCA1/2 mutations.12
To date, the only information available about the real-world experience with talazoparib, 
including patient characteristics, treatment patterns, and clinical outcomes comes from 
compassionate use programs in Turkey, and Russia, and the French temporary authorization 
for use (ATU) program.  Since the approval of talazoparib in the United States (US) in 2018, 
there is no published data about the real-world (RW) experience of talazoparib-treated 
patients with HER2-negative ABC with gBRCA1/2 mutations in the US.     
This approval was based on the Phase 3 EMBRACA trial (NCT01945775), which 
demonstrated that, in comparison to single-agent chemotherapy of the physician’s choice 
(capecitabine, eribulin, gemcitabine, or vinorelbine), talazoparib improved median 
progression-free survival (PFS) by approximately 3 months in adult patients diagnosed with 
HER2-negative ABC with gBRCA1/2 mutations (8.6 months vs 5.6 months [hazard ratio for 
disease progression or death, 0.54]; 95% confidence interval (CI), 0.41 to 0.71; P<0.001).13,14
Additionally, the objective response rate (ORR) was 62.6% in the talazoparib arm versus 
27.2% in the chemotherapy arm (odds ratio (OR), 5.0; 95% CI, 2.9 to 8.8; P<0.001).13,14
Grade 3-4 hematologic adverse events (AEs) occurred in 55% of talazoparib-treated patients
(primarily anemia) versus in 38% of chemotherapy-treated patients, whereas nonhematologic 
Grade 3 adverse events (AEs) occurred in 32% and 38% of patients, respectively.13
To date, there is no published information related to the characteristics, treatment patterns, 
and clinical outcomes of talazoparib-treated patients in the RW US setting. This study aims 
to describe patient demographics, clinical characteristics, clinical outcomes, and treatment 
patterns among patients with gBRCA1/2 mutated HER2- mBC who have received treatment 
with talazoparib.  The EHR data is collected as part of the routine clinical practice and 
enables quick access to rich health information in a timely manner.    

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8. RESEARCH QUESTION AND OBJECTIVES
The following objectives will be assessed among adult patients with HER2-negative mBC with 
gBRCA1/2 mutations treated with talazoparib in first-line or later line of therapy in the RW 
practice setting in the US.
Primary objective
•
Describe time to treatment failure (TTF) with talazoparib for talazoparib-treated patients
 
 
9. RESEARCH METHODS 
9.1. Study design
This is an observational study using de-identified structured EHR data from Flatiron Health 
Analytic Database.  The following table lists 7 key components of the study protocol.
Protocol Component
Description
Eligibility criteria
Talazoparib-treated adult patients with HER2-negative mBC
with gBRCA1/2 mutations identified between 01 January 
2011 to 30 September 2020 from Flatiron Health Analytic 
Database  
Study cohorts
Single cohort study of talazoparib-treated patients
Index date
Date of first talazoparib-containing line of therapy between 
01 January 2018 to 30 September 2020, as defined by the 
Flatiron’s line of therapy business rules
Baseline period
The baseline period will be variable, and it will encompass 
events that occur between 01 January 2011 and the index 
date (e.g., initial breast cancer diagnosis, diagnosis of mBC, 
neoadjuvant/adjuvant therapy)
Follow-up period
From index date to death or end of study follow-up (earliest 
of last patient-level structured or abstracted activity (i.e., the 
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Protocol Component
Description
last record of patient vitals, medication administrations, or
reported laboratory tests/results, or abstracted end date of 
oral medications) or date of data cut-off (30 September 
2020)), whichever occurred first
Primary outcome
TTF for time from talazoparib initiation to discontinuation 
for any reason, including disease progression, treatment 
toxicity, and death. 
 
 
9.2. Setting
The study population includes adult patients with HER2-negative mBC with gBRCA1/2
mutations who initiated talazoparib treatment in first-line or later identified from Flatiron 
Health Analytic Database.  
9.2.1. Inclusion criteria
Patients must meet all of the following inclusion criteria to be eligible for inclusion in the 
study:
1. Diagnosed with breast cancer (ICD-9 174.x or 175.x or ICD-10 C50x) 
2. At least two visits in the Flatiron database on or after 01 January 2011
3. Pathology consistent with breast cancer 
4. Has evidence of stage IV or recurrent metastatic breast cancer with a metastatic 
diagnosis date on or after 01 January 2011.  This includes patients who were 
diagnosed with stage IV at diagnosis or were diagnosed with earlier stage disease, 
then developed a distant metastasis later on, or had recurrence of the disease via a 
distant metastasis 
5. Confirmed receipt of talazoparib as treatment for mBC via abstraction initiated on or 
after 01 January 2018
6. HER2 negative test result on or before the start of patient’s first talazoparib-
containing line of therapy, as defined by Flatiron’s line of therapy rules
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7. BRCA1, BRCA2, BRCA1 and BRCA2 germline mutation, or BRCA germline 
mutation not otherwise specified, identified on or before the start date of patient’s 
first talazoparib-containing line of therapy, as defined by Flatiron’s line of therapy 
business rules 
8. Age 18 or older at the time of first talazoparib-containing line of therapy
9.2.2. Exclusion criteria
Patients meeting any of the following criteria will not be included in the study:
1. Lacking relevant unstructured documents in the Flatiron database for review by the 
abstraction team 
2. Receipt of drug as part of a clinical trial (captured in the database as “clinical study 
drug” without additional information about active ingredient or whether the patient 
received placebo), defined as any non-cancelled order, administration, or oral episode 
for a drug used in a clinical trial, on or prior to start of first talazoparib line of 
therapy, as defined by Flatiron’s line of therapy business rules 
9.3. Variables
Key variables include: 
Variable
Operational definition
Demographic characteristics
Age
Age at index date (date of first talazoparib-containing line 
of therapy in mBC), years
Gender
Male, female, unknown
Hispanic/Latino ethnicity
Yes, No/unknown
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Variable
Operational definition
Time to treatment failure 
(TTF)
Months from start of talazoparib to discontinuation for any 
reason, including disease progression, treatment toxicity, 
and death. 
Patients still on therapy at the end of follow-up (earliest of 
last patient-level structured or abstracted activity (i.e., the 
last record of patient vitals, medication administrations, or 
reported laboratory tests/results, or abstracted end date of 
oral medications) or date of data cut-off (30 September  
2020)) will be censored.
 
 
 
 
 
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9.4. Data sources 
This retrospective observational study will utilize Flatiron Health’s longitudinal, 
demographically, and geographically diverse database derived from EHR data from over 
265 cancer clinics (~800 sites of care) including more than 2.5 million active US cancer
patients available for analysis.  The Flatiron EHRs include the entire patient chart of all 
patients treated in the Flatiron network. 
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Across the clinics in the Flatiron Health Network, data become available in near real time 
after each clinical encounter and contribute to Flatiron’s continuously aggregating centralized 
data set.  Flatiron accesses both structured data (i.e., data points that are organized in a 
predefined manner, such as dropdown fields that reside in an EHR to capture a patient’s 
gender or date of birth or laboratory data) as well as unstructured data (i.e., information that 
is not organized in a preexisting data model, such as free text from a physician note or a 
portable document format (PDF) laboratory report).  The data used in this analysis already 
exist as structured data in an electronic database.  
9.5. Study size
This is a descriptive study and sample size and power calculations are not available.  All 
eligible talazoparib treated patients during the study period will be included in the analysis.  
This will include approximately 40 patients with gBRCA1/2 mutated HER2- mBC who have 
received treatment with talazoparib.  
9.6. Data management
De-identified data are prepared by Flatiron and transferred securely to Pfizer in a standard 
flat file format. Details of de-identification procedure and data management are outlined in 
the Flatiron’s parent database protocol (NEIRB#15-159, “The Flatiron Health Analytic
Database”). All data are stored and backed up on Flatiron’s servers for at least 7 years.
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.
9.8. Analysis overview
Due to the descriptive exploratory nature of this retrospective, observational study, no 
hypotheses have been specified a priori and no formal hypothesis testing will be performed. 
Descriptive analyses will be conducted on variables related to patient demographics, clinical 
characteristics, treatment patterns and history, and clinical outcomes. For time-to-event 
endpoint analyses such as TTF,
the Kaplan-Meier (KM) method will be used, accounting for 
right-censoring. Additionally, depending on sample size, Cox proportional hazards (PH)
models may be used to assess the impact of specific characteristics on time-to-event 
outcomes during post-hoc analysis if sample size allows.
If sample size allows, clinical outcomes will also be reported for post-hoc analytic subgroups 
of interest. Subgroups may include the following and will be determined once data collection 
is complete: patients with HR-positive/HER2-negative mBC and patients with metastatic 
TNBC, patients who received prior platinum therapy in mBC and patients who did not, 
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patients who receive CDK4/6 inhibitors in mBC and those who did not, and subgroups by 
line of therapy of talazoparib initiation.
Post-hoc statistical comparisons between subgroups of interest may be performed if sample 
size allows. The comparison of means (medians where appropriate) and proportions across 
subgroups will be performed using t-tests (Wilcoxon where appropriate) and chi-square tests 
(Fisher exact where cell size is fewer than 5 patients). If post-hoc analyses of subgroups are 
performed, the log-rank test may be used to assess a difference in median time-to-event data 
among subgroups.
Statistical analyses will be performed using SAS v9.4. All tests will be 2-tailed, and the level 
of significance will be set at α=0.05. Statistical tests will only be conducted if the sample size 
is adequate for comparisons. 
9.8.1. Analysis of baseline characteristics
Baseline characteristics of adult patients with HER2-negative mBC and gBRCA1/2
mutations treated with talazoparib monotherapy in a RW practice setting in the US will be 
assessed. Patient demographics and clinical characteristics will be summarized using 
descriptive statistics: mean, standard deviation (STD), median, interquartile range (IQR), and 
minimum/maximum values will be calculated for continuous variables and for categorical 
data, counts and proportions will be calculated. The numbers of missing and unknown 
observations will be described for both categorical and continuous variables. No data 
imputation will be conducted. Patients with missing/unknown data will be reported as such.
9.8.2. Analysis of clinical outcomes 
All categorical and continuous non–time-to-event variables will be analyzed using 
descriptive statistical techniques. For continuous/numeric variables, the mean, STD, median, 
interquartile range (IQR), and minimum/maximum values will be calculated. For categorical 
variables, frequencies and percentages will be provided. 
All time-to-event endpoints will be estimated using univariate analysis and KM methods, as 
appropriate. KM survival curves, KM survival proportions at specified intervals, the number 
of events, and the number of patients censored will be provided. KM-estimated median 
values, first and third quartiles, and 95% CIs around each point estimate will be reported 
when estimable. 
If post-hoc subgroup analyses are performed, the log-rank test may be used to assess a 
difference in median time-to-event data among subgroups. Additionally, depending on 
sample size Cox PH models may be used to assess the impact of specific characteristics on 
time-to-event outcomes during post-hoc analysis.

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Analytic study endpoints will include (but are not limited to) the following:
•
TTF – months from initiation of talazoparib to discontinuation for any reason, 
including disease progression, treatment toxicity, and death
o
Patients still on therapy at the end of follow-up (earliest of last patient-level 
structured or abstracted activity (i.e., the last record of patient vitals, 
medication administrations, or reported laboratory tests/results, or abstracted 
end date of oral medications) or date of data cut-off (30 September 2020)) will 
be censored.
 
 
 
 
 
 
 
 
 
 
 
 
 
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9.9. Quality control
Quality control (QC) will follow the Flatiron’s standard procedure for quality control and 
assurance as described in Flatiron Health Analytic Database Parent Protocol.  QC for 
structured and unstructured data is conducted prior to delivery of each dataset. For each data 
model, Flatiron generates and continually maintains a set of quality standards. These QC 
standards cover themes such as demographics, biomarkers, treatment, therapy shares, and 
treatment length/dosage, and include both medical considerations (e.g., what are expected 
based on the literature and clinical practice) and data considerations (e.g., stability from prior 
months). Issues identified are methodically logged, prioritized, investigated and resolved.
Substantive issues are discussed by the team and a mitigation plan is developed. Any quality 
concerns and the approaches taken to rectify them will be communicated to the sponsor. All 
data undergo statistical review prior to locking the data. Statistical review includes: error log 
search, warning evaluation, logic and critical steps and macro usage.  Queries generated are 
forwarded to the medical lead of the project and resolved prior to the data being locked.
9.10. Limitations of the research methods
One of the main challenges of EHR data is the potential for missing, inaccurate or incomplete 
data (e.g., EHR contains only that a physician prescribed an oral drug but not whether or not 
it was filled/refilled). In addition, the quality of information extracted from the EHR depends 
on the quality of information entered into the EHR by the clinician. Finally, the patient 
populations in the Flatiron database may not be reflective of the general population 
nationally. Some skewing in the data is possible if differences exist between patients in this 
study cohort and general patient population (refer to Flatiron parent protocol). Moreover, the 
sample size of talazoparib-treated patients in this study is small which could affect the 
reliability of study findings.
9.11. Other aspects
Not applicable.
10. PROTECTION OF HUMAN SUBJECTS
All parties will ensure protection of patient personal data and will not include patient names 
on any sponsor forms, reports, publications, or in any other disclosures, except where 
required by laws. In case of data transfer, Pfizer will maintain high standards of 
confidentiality and protection of patient personal data.
Informed consent is not required for this study as it is the secondary use of the existing health 
records and the data is de-identified. There will be no direct involvement of patients and 
patients will receive no direct benefit from participating in the study.
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 

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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, any patient names will be removed and will be replaced by a single, specific, 
numerical code. All other identifiable data transferred to Pfizer or other authorized parties 
will be identified by this single, patient-specific code. In case of data transfer, Pfizer will 
maintain high standards of confidentiality and protection of patients’ personal data consistent 
with the vendor contract, research 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. 
10.3. Institutional review board (IRB)/Independent ethics committee (IEC)
The IRB approval of this observational study with secondary data use from an existing EHR 
database is covered by IRB approval on Flatiron parent protocol.  There are no known risks 
to the patients beyond the potential of loss of confidentiality; all precautions will be 
maintained to protect patient confidentiality and protected health information (PHI) as 
outlined in the parent protocol, NEIRB#15-159. 
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, and informed consent forms, and other relevant documents, 
(e.g., recruitment advertisements), if applicable, 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 Pfizer.
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 the Guidelines for Good Pharmacoepidemiology Practices (GPP) of the 
International Society for Pharmacoepidemiology (ISPE 2008), the Strengthening the 
Reporting of Observational Studies in Epidemiology (STROBE) guidelines, and with the 
ethical principles laid down in the Declaration of Helsinki.

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11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS
This study involves a combination of existing structured data and unstructured data, which 
will be converted to structured form during the implementation of the protocol solely by a 
computer using automated/algorithmic methods, such as natural language processing.
In these data sources, individual patient data are not retrieved or validated, and it is not 
possible to link (i.e., identify a potential association between) a particular product and 
medical event for any individual.  Thus, the minimum criteria for reporting an adverse event 
(AE) (i.e., identifiable patient, identifiable reporter, a suspect product, and event) cannot be 
met.
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
Results from the final analysis may be submitted in the form of peer-reviewed publications 
and/or presented as an abstract or poster at scientific conferences.
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 party responsible for collecting data 
from the participant 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.
ACS. (2021).  American Cancer Society Cancer Statistics Center: Breast Cancer. 
Available from: 
https://cancerstatisticscenter.cancer.org/?_ga=2.72864211.1312339105.1586458273-
885389106.1584627111#!/cancer-site/Breast.
2.
Liang Y, Zhang H, Song X, et al. Metastatic heterogeneity of breast cancer: 
Molecular mechanism and potential therapeutic targets. Semin Cancer Biol. 
2020;60:14-27.
3.
Batra A, Cheung WY. Role of real-world evidence in informing cancer care: lessons 
from colorectal cancer. Curr Oncol. 2019;26(Suppl 1):S53-S56.
4.
Masuda H, Brewer TM, Liu DD, et al. Long-term treatment efficacy in primary 
inflammatory breast cancer by hormonal receptor- and HER2-defined subtypes. Ann 
Oncol. 2014;25(2):384-91.
5.
Testa U, Castelli G, Pelosi E. Breast Cancer: A Molecularly Heterogenous Disease 
Needing Subtype-Specific Treatments. Medical sciences (Basel, Switzerland). 
2020;8(1).
6.
Lee A, Moon BI, Kim TH. BRCA1/BRCA2 Pathogenic Variant Breast Cancer: 
Treatment and Prevention Strategies. Annals of laboratory medicine. 2020;40(2):114-
21.
7.
Patel M, Nowsheen S, Maraboyina S, et al. The role of poly(ADP-ribose) polymerase 
inhibitors in the treatment of cancer and methods to overcome resistance: a review. 
Cell & bioscience. 2020;10:35.
8.
Antolin AA, Ameratunga M, Banerji U, et al. The kinase polypharmacology 
landscape of clinical PARP inhibitors. Scientific reports. 2020;10(1):2585.
9.
Malone KE, Daling JR, Doody DR, et al. Prevalence and predictors of BRCA1 and 
BRCA2 mutations in a population-based study of breast cancer in white and black 
American women ages 35 to 64 years. Cancer Res. 2006;66(16):8297-308.
10.
Kurian AW, Gong GD, John EM, et al. Performance of prediction models for BRCA 
mutation carriage in three racial/ethnic groups: findings from the Northern California 
Breast Cancer Family Registry. Cancer Epidemiol Biomarkers Prev. 
2009;18(4):1084-91.
11.
De Talhouet S, Peron J, Vuilleumier A, et al. Clinical outcome of breast cancer in 
carriers of BRCA1 and BRCA2 mutations according to molecular subtypes. Sci Rep. 
2020;10(1):7073.
12.
FDA. (2018).  U.S. Food and Drug Administration: FDA approves talazoparib for 
gBRCAm HER2-negative locally advanced or metastatic breast cancer. Available 
from: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-
talazoparib-gbrcam-her2-negative-locally-advanced-or-metastatic-breast-cancer.
13.
Litton JK, Rugo HS, Ettl J, et al. Talazoparib in Patients with Advanced Breast 
Cancer and a Germline BRCA Mutation. The New England journal of medicine. 
2018;379(8):753-63.
14.
Zimmer AS, Gillard M, Lipkowitz S, et al. Update on PARP Inhibitors in Breast 
Cancer. Current Treatment Options in Oncology. 2018;19(5):21.

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14. LIST OF TABLES 
Table 1.
Tentative List of CDK4/6 Inhibitors, Chemotherapy, and 
Immunotherapy for the Treatment of HR+/HER2-Negative or 
TNBC Metastatic Breast Cancer a ............................................................28

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Table 1.
Tentative List of CDK4/6 Inhibitors, Chemotherapy, and Immunotherapy 
for the Treatment of HR+/HER2-Negative or TNBC Metastatic Breast 
Cancer a
Drug Name
Brand Name
Type of therapy
Code
Palbociclib
Ibrance
CDK4/6 inhibitor
N/A
Ribociclib
Kisqali
CDK4/6 inhibitor
N/A
Abemaciclib
Verzenio
CDK4/6 inhibitor
N/A
Atezolizumab
Tecentriq
Immunotherapy
J9022
Pembrolizimab
Keytruda
Immunotherapy
J9271
Capecitabine
Xeloda
Chemotherapy
J8520 , J8521
5-fluorouracil
Adrucil
Chemotherapy

J9190
Cisplatin
Platinol
Chemotherapy; 
Platinum therapy

C9418 - Cisplatin (2)
(HCPCS Procedure 
Drug)

J9060 - Cisplatin 10 mg 
injection (2) (HCPCS 
Procedure Drug)

J9062 - Cisplatin 50 mg 
injection (2) (HCPCS 
Procedure Drug)
Carboplatin
Paraplatin
Chemotherapy; 
Platinum therapy
o
J9045 - Injection, 
carboplatin, 50 mg 
(HCPCS Procedure 
Drug)
Cyclophosphamide
Cytoxan
Chemotherapy

C9420 -
Cyclophosphamide (2)
(HCPCS Procedure 
Drug)

C9421 -
Cyclophosphamide (2)
(HCPCS Procedure 
Drug)

J8530 -
Cyclophosphamide oral 
25 mg (2) (HCPCS 
Procedure Drug)

J9070 -
Cyclophosphamide 100 
mg inj (2) (HCPCS 
Procedure Drug)

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Table 1.
Tentative List of CDK4/6 Inhibitors, Chemotherapy, and Immunotherapy 
for the Treatment of HR+/HER2-Negative or TNBC Metastatic Breast 
Cancer a
Drug Name
Brand Name
Type of therapy
Code

J9080 -
Cyclophosphamide 200 
mg inj (2) (HCPCS 
Procedure Drug)

J9090 -
Cyclophosphamide 500 
mg inj (2) (HCPCS 
Procedure Drug)

J9091 -
Cyclophosphamide 1.0 
grm inj (2) (HCPCS 
Procedure Drug)

J9092 -
Cyclophosphamide 2.0 
grm inj (2) (HCPCS 
Procedure Drug)

J9093 -
Cyclophosphamide 
lyophilized (2) (HCPCS 
Procedure Drug)

J9094 -
Cyclophosphamide 
lyophilized (2) (HCPCS 
Procedure Drug)

J9095 -
Cyclophosphamide 
lyophilized (2) (HCPCS 
Procedure Drug)

J9096 -
Cyclophosphamide 
lyophilized (2) (HCPCS 
Procedure Drug)

J9097 -
Cyclophosphamide 
lyophilized (2) (HCPCS 
Procedure Drug)

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Table 1.
Tentative List of CDK4/6 Inhibitors, Chemotherapy, and Immunotherapy 
for the Treatment of HR+/HER2-Negative or TNBC Metastatic Breast 
Cancer a
Drug Name
Brand Name
Type of therapy
Code
Docetaxel
Chemotherapy

J9170 - INJECTION, 
DOCETAXEL, 20 MG
(HCPCS Procedure 
Drug)

J9171 - Injection, 
docetaxel, 1 mg (HCPCS 
Procedure Drug)
Doxorubicin
Taxotere
Chemotherapy

C9415 - Doxorubicin (2)
(HCPCS Procedure 
Drug)

J9000 - Doxorubicin hcl 
injection (2) (HCPCS 
Procedure Drug)

J9001 - Doxorubicin hcl
liposome inj (2) (HCPCS 
Procedure Drug)

Q2050 - Doxorubicin inj 
10mg (2) (HCPCS 
Procedure Drug)
Epirubicin
Ellence
Chemotherapy

J9178
Eribulin
Halaven
Chemotherapy

C9280 - Injection, 
eribulin mesylate (2)
(HCPCS Procedure 
Drug)

J9179 - Eribulin mesylate 
injection (2) (HCPCS 
Procedure Drug)
Gemcitabine
Gemzar
Chemotherapy
J9201
Ixabepilone
Ixempra
Chemotherapy
J9207
Methotrexate
NA
Chemotherapy
J8610, J9250, J9260, 
Mitomycin
NA
Chemotherapy
J9280
Mitoxantrone
Novantrone
Chemotherapy
J9293
Nab-paclitaxel
Abraxane
Chemotherapy
No code specific to 
Abraxane

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Table 1.
Tentative List of CDK4/6 Inhibitors, Chemotherapy, and Immunotherapy 
for the Treatment of HR+/HER2-Negative or TNBC Metastatic Breast 
Cancer a
Drug Name
Brand Name
Type of therapy
Code
Paclitaxel
Taxol
Chemotherapy

C9127 - Paclitaxel (2)
(HCPCS Procedure 
Drug)

C9431 - Paclitaxel (2)
(HCPCS Procedure 
Drug)

I - PACLITAXEL NO 
STRENGTH (Uncoded 
Product Identifier)

J9264 - Paclitaxel protein 
bound (2) (HCPCS 
Procedure Drug)

J9265 - Paclitaxel 
injection (2) (HCPCS 
Procedure Drug)
J9267 - Paclitaxel injection 
(2) (HCPCS Procedure 
Drug)
Vinorelbine
Navelbine
Chemotherapy

J9390
a The final list of chemotherapies, CDK4/6 inhibitors, and immunotherapies will be determined after 
evaluating the administered medications and oral therapies among eligible mBC patients.
15. LIST OF FIGURES
Not applicable.
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS
None.
ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS
Not applicable.
ANNEX 3. ADDITIONAL INFORMATION
Not applicable.