Real-World Patient Characteristics, Treatment Patterns, and Clinical Outcomes Among Talazoparib-Treated Patients With HER2-Negative, Locally Advanced or Metastatic Breast Cancer and Germline BRCA1/2 Mutations: US Chart Review
Conditions: Breast Cancer
Sponsor: Pfizer

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NON-INTERVENTIONAL (NI) STUDY PROTOCOL
Study information
Title
Real-World Patient Characteristics, Treatment Patterns, 
and Clinical Outcomes Among Talazoparib-Treated 
Patients with HER2-Negative, Locally Advanced or 
Metastatic Breast Cancer and Germline BRCA1/2
Mutations: US Chart Review
Protocol number
C3441053
Protocol version identifier
1.0
Date
22 June 2021
Active substance
Talazoparib
Medicinal product
TALZENNA®
Research question and 
objectives
Primary objectives: 
The following primary objectives will be assessed among 
adult patients with human epidermal growth factor 
receptor 2 (HER2)-negative advanced breast cancer 
(ABC) with germline breast cancer susceptibility gene 1
or 2 (gBRCA1/2) mutations treated with talazoparib in 
the real-world (RW) practice setting in the United States 
(US):
1. Describe demographic and clinical characteristics.
2. Describe patterns of treatment with talazoparib 
monotherapy 
 
 
3. Describe RW clinical outcomes of talazoparib 
monotherapy-treated patients, including:
a.
Time to treatment failure (TTF) for 
talazoparib 
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b. RW progression-free survival (rwPFS) 
 
d. RW overall response rate (rwORR) 
f.
Time to chemotherapy administered 
following talazoparib
 
 
 
 
 
 
 
 
 
Authors
 MA 
 
Pfizer, Inc
 PhD
 MPH
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
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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.......................................................................................................4
2. LIST OF ABBREVIATIONS................................................................................................6
3. RESPONSIBLE PARTIES..................................................................................................10
4. ABSTRACT.........................................................................................................................11
5. AMENDMENTS AND UPDATES.....................................................................................15
6. MILESTONES.....................................................................................................................16
7. RATIONALE AND BACKGROUND................................................................................17
8. RESEARCH QUESTION AND OBJECTIVES .................................................................18
8.1. Primary population objectives:................................................................................18
9. RESEARCH METHODS ....................................................................................................19
9.1. Study design ............................................................................................................19
9.1.1. Other Aspects of Study Design...................................................................21
9.2. Setting......................................................................................................................21
9.2.1. Inclusion criteria .........................................................................................22
9.2.2. Exclusion criteria........................................................................................23
9.3. Variables..................................................................................................................23
9.3.1. Provider/Practice Characteristics................................................................23
9.3.2. Patient Demographic & Clinical Characteristics........................................24
9.3.3. Talazoparib Treatment Patterns..................................................................24
9.3.4. Treatment Patterns Prior to/Following Talazoparib ...................................25
9.3.5. Clinical Outcomes of Talazoparib Therapy................................................25
9.4. Data sources ............................................................................................................26
9.5. Study size ................................................................................................................26
9.6. Data management....................................................................................................27
9.6.1. Case report forms (CRFs) /Electronic data record .....................................27
9.6.2. Record retention..........................................................................................28
9.7. Data analysis ...........................................................................................................28
9.7.1. Analysis overview ......................................................................................28
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9.7.2. Analysis of baseline characteristics in the primary analysis 
population ........................................................................................................29
9.7.3. Analysis of clinical outcomes in the primary analysis population .............30
9.7.4. Subgroup analyses for the primary analysis population.............................31
9.8. Quality control.........................................................................................................32
9.9. Strengths and limitations of the research methods..................................................33
9.9.1. Strengths .....................................................................................................33
9.9.2. Limitations..................................................................................................34
9.10. Other aspects .........................................................................................................35
10. PROTECTION OF HUMAN SUBJECTS ........................................................................35
10.1. Patient information................................................................................................35
10.2. Patient consent.......................................................................................................35
10.3. Institutional review board (IRB)/Independent ethics committee (IEC)................36
10.4. Ethical conduct of the study..................................................................................36
11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................36
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........37
13. REFERENCES ..................................................................................................................37
14. LIST OF TABLES.............................................................................................................38
15. LIST OF FIGURES ...........................................................................................................39
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS.........................................................39
ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS .........................................39
ANNEX 3. ADDITIONAL INFORMATION.........................................................................39
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2. LIST OF ABBREVIATIONS
Abbreviation
Definition
ABC
Advanced breast cancer
AE
Adverse event
AEM
Adverse event monitoring
BC
Breast cancer
BRCA1
Breast cancer susceptibility gene 1
BRCA2
Breast cancer susceptibility gene 2
CDK 
Cyclin-dependent kinase 
CHSS
Cardinal Health Specialty Solutions
CI
Confidence interval
CNS
Central nervous system
CR
Complete response
CRF
Case report form
CSA
Clinical study agreement
ECOG-PS
Eastern Cooperative Oncology Group performance status
eCRF
Electronic case report form
EHR
Electronic health record
ER
Estrogen receptor
ESR1
Estrogen receptor 1
FDA
Food and Drug Administration
FISH
Fluorescent in situ hybridization
gBRCA1/2
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Abbreviation
Definition
GPO
Group purchasing organization
GPP
Good Pharmacoepidemiology Practices
HCP
Healthcare professional
HER2
Human epidermal growth factor receptor 2
HIPAA
Health Insurance Portability and Accountability Act
HR
Hormone receptor
IEC
Independent ethics committee
IHC
Immunohistochemistry
IQR
Interquartile range
IRB
Institutional review board
ISPE
International Society for Pharmacoepidemiology
KM
Kaplan-Meier
KPS
Karnofsky performance status
LOT
Line of therapy
NIS
Non-interventional study
OPEN
Oncology Provider Extended Network
OR
Odds ratio
ORR
Objective response rate
PARP
Poly(adenosine diphosphate–ribose) polymerase
PD
Progressive disease
PD-1
Programmed cell death protein 1
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Abbreviation
Definition
PD-L1
Programmed death ligand 1
PFS
Progression-free survival
PgR
Progesterone receptor
PH
Proportional hazards
PHI
Protected health information
PIK3CA
Phosphoinositide 3-kinase
PR
Partial response
PV
Pharmacovigilance
QA
Quality assurance
QC
Quality control
RW
Real-world
rwORR
Real-world overall response rate
rwPFS
Real-world progression-free survival
SAE
Serious adverse event
SAP
Statistical analysis plan
SD
Stable disease
STD
Standard deviation
STROBE
Strengthening the Reporting of Observational Studies in 
Epidemiology
TNBC
Triple-negative breast cancer
TTF
Time to treatment failure
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Abbreviation
Definition
UAT
User acceptance testing
US
United States
YRR
Your Reporting Responsibilities (Pfizer AE training)

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3. RESPONSIBLE PARTIES
Principal Investigator(s) of the Protocol
Name, degree(s)
Job Title
Affiliation
Address
 
MA
             
 
Pfizer, Inc.
235 East 42nd 
Street New York,
NY 10017
 
PharmD, RPh, 
MPH, 
             
 
 
 
Pfizer, Inc.
235 East 42nd 
Street New York, 
NY 10017
 
PhD, RN
       
Pfizer, Inc.
235 East 42nd 
Street New York, 
NY 10017
 PhD
Senior Scientist, 
 
 
 
 
MPH
Scientist,            
 
 
 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
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4. ABSTRACT
Real-World Patient Characteristics, Treatment Patterns, and Clinical Outcomes Among 
Talazoparib-Treated Patients with HER2-Negative, Locally Advanced or Metastatic Breast 
Cancer and Germline BRCA1/2 Mutations: US Chart Review
Version 1, 22 June 2021
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, there is no published information about the characteristics, 
treatment patterns, and clinical outcomes of talazoparib-treated patients in the real-world (RW) 
United States (US) setting. The RW assessment of ABC patients with gBRCA1/2 mutations 
treated with talazoparib since its approval in 2018 will provide information about the patient 
characteristics, treatment patterns, and clinical outcomes of talazoparib-treated patients in the 
US.
Research question and objectives
Primary objectives: 
The following primary objectives will be assessed among adult patients with HER2-negative 
ABC with gBRCA1/2 mutations treated with talazoparib in the RW practice setting in the US.
1. Describe demographic and clinical characteristics.
2. Describe patterns of treatment with talazoparib monotherapy 
 
 
3. Describe RW clinical outcomes of talazoparib monotherapy-treated patients, including:
a.
Time to treatment failure (TTF) for talazoparib 
b. RW progression-free survival (rwPFS) 
d. RW overall response rate (rwORR) 
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f.
Time to chemotherapy administered following talazoparib
 
 
 
 
 
 
Study design
This study consists of a retrospective, multi-site, patient-level medical chart review of US adult 
ABC patients who initiated talazoparib on or after October 16, 2018 and were managed by 
participating providers from Cardinal Health’s Oncology Provider Extended Network (OPEN). 
A minimum of 6 months follow-up is required unless the patient died within this follow-up 
period. 
Population
Data from primary 
 populations will be analyzed 
 
Primary population: 
1. HER2-negative ABC patients with gBRCA1/2 mutations treated with talazoparib 
monotherapy initiated on or after October 16, 2018 and ≥18 years of age at initiation 
of talazoparib. 
All patients in the primary population will have had a minimum of 6 months follow-up time 
after initiation of talazoparib unless the patient died within this follow-up period. No patients
will have participated in any breast cancer (BC) clinical trial after initiation of talazoparib, 
been treated with a PARP inhibitor as neoadjuvant/adjuvant therapy, have unknown 
gBRCA1/2 status, or have been diagnosed with any other malignancy within the 5 years prior 
to data collection. 
 
 
 
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Variables
Patient demographics, clinical characteristics, patterns of treatment with talazoparib and 
therapy administered prior to and following talazoparib, and clinical outcomes will be collected 
and analyzed 
 for primary and 
 cohort . 
Data sources
The patient’s treating physician will abstract data from the patient’s electronic health record 
(EHR) into the data capture forms. All study data are secondary. Providers will be trained on 
data collection to ensure accuracy and reliability. No protected health information (PHI), 
except for dates of diagnosis, treatment, and outcomes, will be collected. The patient’s EHR 
data will not be shared directly with Cardinal Health Specialty Solutions (CHSS) or Pfizer. 
Study size
The total targeted sample sizes for the 
 primary and 
 population  are as 
follows: 
Primary population: 
1. Approximately 110 HER2-negative ABC patients with gBRCA1/2 mutations treated 
with talazoparib. 
 
 
 
 
An estimated data exclusion rate of 3% following quality control (QC) processes is expected. 
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Data analysis
Primary 
 cohorts will be delineated and analyzed 
 
 Descriptive analyses will be conducted on patient 
demographics, clinical characteristics, treatment patterns and history, biomarker status (e.g., 
mutation of  BRCA1 or BRCA2), and clinical outcomes. For 
 rwPFS, and all other time-
to-event endpoint analyses, the Kaplan-Meier (KM) method will be used, accounting for right-
censoring. To assess differences in the odds of disease response, logistic regression may be 
used to calculate the odds ratio (OR) and associated P-values 
 
 Cox proportional hazards (PH) regression 
will be applied for time-to-event data analysis. If post-hoc analyses are performed, the log-
rank test may be used to assess a difference in median time-to-event data among subgroups for 
the primary analysis cohort. 
 
 
The comparison of means (medians where appropriate) and proportions 
across cohorts will be performed using t-tests (Wilcoxon where appropriate) and chi-square 
tests (Fisher exact where cell size is fewer than 5 patients). 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. 
If sample size allows, clinical outcomes will also be reported for analytic subgroups of interest 
 for the primary population 
 
 Subgroups may include the following, to be determined once data collection is 
complete: hormone receptor (HR)-positive/HER2-negative patients and patients with triple-
negative BC (TNBC),
 
 
 
 
 
 
Milestones
Start of data collection: Q3 2021
End of data collection: Q3 2021
Final study report: Q4 2021
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5. AMENDMENTS AND UPDATES
None.

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6. MILESTONES
Milestone
Planned date
Completion of feasibility assessment
01 March 2021
Project kickoff
10 March 2021
Study protocol 
26 March 2021
Study protocol finalization/approval
Q2 2021
Case report form (CRF) 
Q2 2021
CRF finalization/approval 
Q2 2021
Institutional review board (IRB) 
preparation/submission/approval 
Q3 2021
Electronic CRF (eCRF) programming & testing completion
Q3 2021
eCRF pre-test completion/eCRF finalized
Q3 2021
Statistical Analysis Plan (SAP) & table shells
Q3 2021
SAP & table shells finalization/approval
Q3 2021 
Start of data collection
Q3 2021
End of data collection
Q3 2021
Analytic/Clinical data quality review completion
Q4 2021
Data analysis completion
Q4 2021
Summary report
Q4 2021
Final study report
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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 
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 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 having gBRCA1/2 mutations.12 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. 
 
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8. RESEARCH QUESTION AND OBJECTIVES
Among patients managed by oncologists in the Cardinal Health OPEN, this study aims to
achieve the following research objectives. 
 
8.1. Primary population objectives: 
The following primary objectives will be assessed among adult patients with HER2-negative 
ABC with gBRCA1/2 mutations treated with talazoparib monotherapy in the RW US practice 
setting:
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1. Describe demographic and clinical characteristics.
2. Describe patterns of treatment with talazoparib monotherapy 
 
 
3. Describe RW clinical outcomes of talazoparib monotherapy-treated patients, including:
a.
Time to treatment failure (TTF) for talazoparib 
b. RW progression-free survival (rwPFS) 
d. RW overall response rate (rwORR) 
f.
Time to chemotherapy administered following talazoparib
 
 
 
 
 
 
9. RESEARCH METHODS 
9.1. Study design
To achieve the research objectives described above, retrospective, multi-site, medical chart 
review will be conducted of study-eligible, talazoparib-treated ABC patients at community 
oncology clinics in the US. Providers in the OPEN who have previously indicated treating 
patients meeting the study selection criteria will be recruited and invited to participate (see 
Section 8.2. for further details) in the patient identification and data abstraction. Additional 
providers in OPEN may be recruited to aid in patient recruitment. All study data are secondary 
and will have been collected retrospectively from existing clinical data originally collected as 
part of routine care.
Patient eligibility will be confirmed by the treating physician. Providers will abstract de-
identified patient-level data necessary to achieve the research objectives into an eCRF. No 
protected health information (PHI), except for dates of diagnosis, treatment, and outcomes, 
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will be collected. The patient’s electronic health record (EHR) data will not be shared directly 
with Cardinal Health or Pfizer.
Data related to RW patient characteristics, treatment patterns, and clinical outcomes among 
talazoparib-treated patients will be captured and reported separately for the following 3 distinct 
cohorts of patients (cohorts will never be combined during analysis): 
One primary population:  
!
HER2-negative ABC patients with gBRCA1/2 mutations treated with talazoparib 
monotherapy initiated on or after October 16, 2018 and ≥18 years of age at initiation 
of talazoparib. 
 
 
 
 
 
If sample size allows, clinical outcomes will also be reported for post-hoc analytic subgroups 
of interest 
 for the primary population 
 
 Subgroups may include the following, to be determined once data 
collection is complete: patients with HR-positive/HER2-negative BC and patients with TNBC, 
 
 
 
 
  
 
For all study-eligible patients, talazoparib treatment for ABC will have been initiated on or 
after October 16, 2018 and a minimum of 6 months follow-up is required unless the patient 
died within this follow-up period. Data collection is scheduled to begin in August 2021 and 
end in September 2021. The pre-index period will be variable and will encompass events and 
data occurring prior to the initiation of talazoparib treatment (e.g., initial breast cancer 
diagnosis, initial diagnosis of ABC, neoadjuvant/adjuvant therapy). Index date is defined as 
the date of initiation of talazoparib. The index period is defined as the period of time spanning 
the initiation of talazoparib on or after October 16, 2018 and the date of last follow-up. A 
minimum of 6 months follow-up after initiation of talazoparib is required for all patients, with 
the exception of patients who died within the follow-up period. The exact length of follow-up 
will be variable between patients (Figure 1).
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F1
9.1.1. Other Aspects of Study Design
Although data on AEs will not be collected in the CRF, all clinicians who participate in this 
research will be required to complete Pfizer training related to the identification and reporting 
of AEs/serious adverse events (SAEs). AE/SAE training materials will be provided to the 
participating clinicians prior to any data collection. Providers will complete the AE/SAE 
training and electronically sign the certificate.
9.2. Setting
Providers who participated in the prior related feasibility surveys and short chart review study 
and who reported having treated potentially eligible patients will be invited to participate in 
this study. These providers volunteered to participate in the feasibility surveys and/or short 
chart review after receiving invitations to participate that were sent out to a subset 
(approximately 800) of CHSS’ OPEN providers. Additional physicians from the OPEN may 
also be recruited to achieve the targeted patient numbers. Recruited providers who volunteer 
to participate in this study will identify patients meeting the study selection criteria through a 
series of screener questions. Additionally, these physicians will provide an estimate of their 
total eligible patient population.
As of 2020, the OPEN community comprised more than 7,000 unique providers in oncology, 
hematology, and urology across the US who had participated in Cardinal Health internal 
market research, educational summits, industry-sponsored research, or whose practices had 
Figure 1. Study period 
16-Oct-2018
6 months prior to 
eCRF launch date
Index period
Initiation of talazoparib therapy
Potential follow-up period
Data collection       
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used the Cardinal Health proprietary point-of-care claims remittance software over the past 7 
years. Of the providers, approximately 800 composed the RW research community, and 300 
unique investigators have contributed patient-level data to retrospective chart abstraction 
research since 2016. OPEN is group purchasing organization (GPO)- and EHR- software 
agnostic. Providers are predominantly in community practices (>75%), ranging in size from 
solo practitioners to hospital systems, and participate in centralized institutional board review 
(IRB) approval. Because OPEN is a provider-level (as opposed to site-based) community, 
CHSS can obtain large, representative samples of patients and collect detailed clinical data 
from their treating providers. Due to the purposive sampling that selects physicians and 
patients based on pre-specified selection criteria, however, this study may not be representative 
of all ABC patients treated with talazoparib or of all providers treating these types of patients. 
To be eligible for participation in this research study, a board-certified hematologist/oncologist
must have treated or be treating at least 1 ABC patient meeting the eligibility criteria for the 
study, agree to participate in a study sponsored by Pfizer, and agree to complete and adhere to 
the Pfizer AE/SAE reporting protocols. Providers must also be able to participate in research 
monitored by a central IRB. No site-specific IRB approval will be sought, and providers 
requiring this approval will not be eligible. 
After IRB approval of the research protocol, the eCRF will be pre-tested with 2 providers. Data 
collected as part of the pre-test will not be used in the final analytic dataset. After testing and 
revisions (if necessary), providers from OPEN will be contacted and asked to participate in the 
research. Data collection will be conducted over the course of 4 weeks. Providers will submit 
a maximum of 10 eCRFs each (the maximum number of eCRFs per provider may be increased, 
if necessary, to achieve target patient numbers following pre-approval from Pfizer). Physicians 
will be asked to identify all eligible patients, report the total number of eligible patients, and 
chronologically select consecutive eligible patients, starting with the earliest eligible.
9.2.1. Inclusion criteria
Patients must meet all of the following inclusion criteria to be eligible for inclusion in the 
study:

≥18 years of age at initiation of talazoparib

A minimum of 6 months follow-up time after initiation of talazoparib unless the patient 
died within this follow-up period
For HER2-negative patients with gBRCA1/2 mutations (population for primary analysis, 
approximately 110 patients):

Diagnosed with HER2-negative ABC

gBRCA1/2 mutation(s)

Treatment with talazoparib monotherapy initiated on or after October 16, 2018 

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9.2.2. Exclusion criteria
Patients meeting any of the following criteria will not be included in the study:
!
Participation in any BC clinical trial after initiation of talazoparib
!
Treatment with a PARP inhibitor as neoadjuvant/adjuvant therapy
!
gBRCA1/2 or HER2 status unknown
!
Diagnosis of any other malignancy, except carcinoma in situ or nonmelanoma skin 
cancer, within the 5 years prior to data collection
9.3. Variables
The following subsections summarize the key variables to be collected from patient medical 
records via the eCRF by their treating providers. Detailed definitions will be included in the 
statistical analysis plan (SAP) and case report form (CRF) documents, which may include 
variables not listed below.
9.3.1. Provider/Practice Characteristics
!
Primary practice setting (e.g., small private practice)
!
Whether physician is practicing in a BC-only clinical practice
!
US region
!
Years in practice
!
Specialty
!
Total number of talazoparib-treated patients who meet study eligibility requirements
!
Estimated ABC patient volumes in study period:
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o
overall 
o
talazoparib-treated
o
HER2-negative

with gBRCA1/2 mutation(s)
9.3.2. Patient Demographic & Clinical Characteristics
!
Sex at birth, year of birth, payer, state of residence, race/ethnicity
!
Family history of BRCA-related cancers, if known (e.g., breast, ovarian, fallopian tube, 
peritoneal, prostate, pancreatic, gastric, colon)
!
Biomarker testing (findings, type, lab, test dates), which may include 
immunohistochemistry (IHC)
score, test type (e.g., IHC/fluorescent in situ 
hybridization [FISH]), name of lab performing tests, sample used for BRCA1/2 testing 
(e.g., blood, saliva, tumor tissue), somatic or germline test for BRCA1/2, and dates of 
tests for the following:
o
BRCA1/2 mutation analysis
o
ER expression analysis
o
PgR expression analysis
o
Estrogen receptor 1 (ESR1) expression analysis
o
HER2 expression analysis
o
PD-L1 expression analysis
o
Phosphoinositide 3-kinase (PIK3CA) mutation analysis
!
Stage/date at initial diagnosis of BC
!
Date of ABC diagnosis
!
Sites of metastasis at initiation of therapy
!
Comorbidities (included in the Charlson Comorbidity Index)
!
Eastern Cooperative Oncology Group performance status (ECOG-PS)
!
Karnofsky performance status (KPS)
9.3.3. Talazoparib Treatment Patterns
!
Start/stop dates of therapy
 
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9.3.4. Treatment Patterns Prior to/Following Talazoparib
!
Total lines of therapy (LOT) in the ABC setting:
o
For the purposes of this study, one LOT ends when the patient discontinued 
treatment with a regimen; if a drug was added to the ongoing treatment, this 
should be considered a new LOT. If a drug within a combination is held or 
discontinued, this should not be considered a new LOT.
!
Prior platinum- or non-platinum-based chemotherapy, hormone therapy, HER2-
directed therapy, or immunotherapy in the neoadjuvant/adjuvant setting:
!
Pre- and post-talazoparib systemic therapies in the ABC setting:
o
Start/stop dates
9.3.5. Clinical Outcomes of Talazoparib Therapy
Collected data elements:
!
Provider-reported/charted best response to therapy (i.e., complete response [CR], 
partial response [PR], stable disease [SD], progressive disease [PD], not evaluable, too
early to tell, or unable to substantiate) during talazoparib therapy
!
Date of initial response during talazoparib therapy
!
Date of disease progression/recurrence during talazoparib therapy
!
Date of last follow-up
!
Date of death, if applicable
Clinical outcomes that will be assessed based on the collected data elements:
!
TTF – time from initiation of talazoparib to discontinuation for any reason, including 
disease progression, treatment toxicity, and death
!
rwPFS – time from initiation of talazoparib to charted disease progression based on 
radiographic imaging or death from any cause, whichever occurs first
 
!
rwORR – sum of complete and partial responses divided by all patients with reported 
disease response assessment
 
!
Time to chemotherapy – time from initiation of talazoparib to initiation of subsequent 
chemotherapy
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9.4. Data sources 
Data will be abstracted and entered into the eCRFs by patients’ treating physicians within the 
OPEN. The source documents are the patient chart/medical record data housed within the 
EHRs and accessed by the participating providers. Data abstracted into the eCRFs must match 
those charts. To adhere to Pfizer’s requirements for non-interventional studies (NIS) collecting 
data for patients treated with a Pfizer product, all providers who wish to participate will 
complete the required Pfizer pharmacovigilance (PV) training for reporting of AEs.
Through the chart review approach, data elements contained in unstructured fields of the EHR
(e.g., clinical progress notes, radiographic scans/reports, pathology reports) or those elements 
requiring a provider’s interpretation (e.g., date of progression) can be collected. The eCRF is 
a custom data abstraction tool allowing the provider chart abstractor to input de-identified data 
directly from the patient EHR into a secure, web-based platform. The data elements that can 
be collected are limited by the length of time required for the participating provider to conduct 
the data abstraction, which may vary depending upon the complexity of data elements required 
and the patient’s health record. Based on the study objectives, a preliminary outline of key 
variables and datapoints to be abstracted into the eCRF by participating physicians is included 
in Section 9.3 above. 
No source document verification can be conducted by CHSS; however, data quality control 
(QC), quality assurance (QA), and validation processes will be performed as described. These 
processes and systems are vetted during field testing with volunteer physicians, as described 
in Section 9.8.
9.5. Study size
As there are no a priori hypotheses specified, sample size calculations are not applicable, and 
power calculations were not performed. To estimate the numbers of potentially available 
eCRFs, an initial feasibility survey and subsequent, in-depth feasibility/short CRF study were 
conducted that identified the numbers of HER2-negative or HER2-positive ABC patients with 
gBRCA1/2 mutations treated with talazoparib since 2018 by providers in the Cardinal Health 
OPEN. In the short CRF study, providers were required to confirm whether germline mutations 
were detected in BRCA1, BRCA2, or both, as well as the sample type used to detect gBRCA 
mutation(s). Participating physicians were also required to provide other basic demographic, 
clinical, and treatment descriptors of patients. 
 
 For the main analysis aimed to address the primary objectives of 
this study, sample size will be approximately 110 patients. 
 
 
 
 
 
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9.6. Data management 
Patient-level data are entered by the treating provider into the eCRF, a custom data abstraction 
tool for capturing deidentified patient-level data directly into a secure, web-based survey 
platform (Qualtrics). The eCRF structure and format are designed to allow providers to 
efficiently move through the EHR while documenting the patient journey throughout the 
course of disease. The eCRF conforms to the rules and regulations of the Health Insurance 
Portability and Accountability Act (HIPAA) of 1996 governing the abstraction and storage of 
PHI. Limited and necessary to achieve study objectives PHI (e.g., start and end of treatment 
dates, date of death) will be collected in the course of the chart review or stored in the eCRF.
The CHSS research team is responsible for the programming, testing, and hosting of data from 
submitted eCRFs, and all data are stored on encrypted, password-protected, and HIPAA-
compliant servers housed within the Cardinal Health electronic data storage infrastructure.
Participating physicians will be asked to complete the chart review individually, meaning that 
site research staff or support staff will not complete any data abstraction. Physicians are 
instructed to consult all available sources and indicate whether data points have been 
substantiated by source materials in the EHR. The study variables that can be collected are 
limited to those that can be captured within the allotted 45 to 60 minutes.
Following protocol finalization, a text version of the CRF will be created, and once finalized, 
an eCRF will be programmed in Qualtrics. Variables are captured in numeric and text format, 
as appropriate, and grouped according to the study objectives as described in the protocol. The 
Qualtrics interface used for data entry and management provides screens for data entry and 
includes study-specific programming checks to help control for data quality, consistency, and 
validity. No source document verification can be conducted by Cardinal Health; however, data 
QC, QA, and validation processes will be performed as described. The raw data entered into 
Qualtrics will be vetted through QA, QC, and validation procedures as described in Section 
9.8, and a CHSS analyst will export them into SAS v9.4 for data transformation and analysis, 
which will be used for all manipulations of data. Pfizer will not have access to the individual 
data collected.
9.6.1. Case report forms (CRFs) /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 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 

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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 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 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 CHSS 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 or as 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 
9.7.1. Analysis overview
Detailed methodology for summary and statistical analyses of data collected in this study will 
be documented in the SAP, which will be dated, filed, and maintained by the sponsor. Due to 
the descriptive 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 provider characteristics, patient
demographics, clinical characteristics, treatment patterns and history, biomarker status, and 
clinical outcomes. For 
 rwPFS, and all other time-to-event endpoint analyses, the Kaplan-
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Meier (KM) method will be used, accounting for right-censoring. To assess differences in the 
odds of disease response, logistic regression may be used to calculate the OR and associated 
P-values 
 
 If 
post-hoc analyses are performed, the log-rank test may be used to assess a difference in median 
time-to-event data among subgroups for the primary analysis cohort.
 
 
The comparison of means (medians 
where appropriate) and proportions across cohorts will be performed using t-tests (Wilcoxon 
where appropriate) and chi-square tests (Fisher exact where cell size is fewer than 5 patients). 
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. Primary 
 cohorts will be delineated and analyzed 
 as follows 
 The primary 
analysis cohort will consist of adult HER2-negative ABC patients with gBRCA1/2 mutations 
treated with talazoparib monotherapy in a RW practice setting in the US.
 
 
If sample size allows, clinical outcomes will also be reported for post-hoc analytic subgroups 
of interest only for the primary population 
 
 Subgroups may include the following and will be determined once 
data collection is complete: patients with HR-positive/HER2-negative BC and patients with 
TNBC, 
 
 
 
 
 
Post-hoc statistical comparisons between subgroups of interest in the primary analysis cohort 
may be performed if sample size allows, using chi-square tests and t-tests or their non-
parametric equivalents. 
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. 
9.7.2. Analysis of baseline characteristics in the primary analysis population
Baseline characteristics of adult HER2-negative ABC patients with gBRCA1/2 mutations 
treated with talazoparib monotherapy in a RW practice setting in the US will be assessed in 
the primary analysis. Patient demographics and clinical characteristics will be summarized 
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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.
9.7.3. Analysis of clinical outcomes in the primary analysis population
All categorical and continuous non–time-to-event variables collected for the primary analysis 
population of adult HER2-negative ABC patients with gBRCA1/2 mutations treated with 
talazoparib monotherapy in a RW practice setting in the US 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 analyses are performed, the log-rank test may be used to assess a difference in 
median time-to-event data among subgroups for the primary analysis cohort. To assess whether 
differences exist in the odds of disease response to treatment, the OR and associated P-values
may be calculated, 
 
 
Analytic study endpoints for the primary analysis population will include (but are not limited 
to) the following:
!
TTF – time from initiation of talazoparib to discontinuation for any reason, including 
disease progression, treatment toxicity, and death
o
Patients still on therapy at last encounter will be censored at last encounter date
!
rwPFS – time from initiation of talazoparib to disease progression based on 
radiographic imaging or death from any cause, whichever occurs first
o
Patients who discontinued talazoparib for a reason other than progression or 
death will be censored at talazoparib discontinuation date. Patients still 
receiving talazoparib at last encounter will be censored on date of last 
encounter.
 
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o
Patients who are known to be alive or lost to follow-up will be censored on the 
date of last encounter
!
rwORR – sum of patients with reported complete and partial responses to talazoparib 
divided by all patients assessed for disease response
 
 
!
Time to chemotherapy – time from initiation of talazoparib to initiation of subsequent 
chemotherapy
9.7.4. Subgroup analyses for the primary analysis population
All or a selected set of variables may also be reported for subgroups of patient cohorts of the 
primary analysis population of adult HER2-negative ABC patients with gBRCA1/2 mutations 
treated with talazoparib monotherapy in a RW practice setting in the US. If sample size allows, 
clinical outcomes will also be reported for post-hoc analytic subgroups of interest only for the 
primary population 
 
Subgroups may include the following, to be determined once data collection is complete: 
!
HR-positive/HER2-negative BC
!
TNBC
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9.8. Quality control
CHSS will be responsible for the programming, testing, and hosting of data from submitted 
CRFs. Testing includes ensuring functionality across web-based user environments, looping 
logic to ensure proper alignment of data-related fields (required responses to certain fields prior 
to entering data into subsequent field), and other programmatic checks to reduce input of 
erroneous data (such as specifying maximums for year of birth or initiation of index treatment 
within the dates of the enrollment period). 
In addition, the eCRF will be field-tested with 2 providers to ensure its functionality, the correct 
interpretation of the questions in relation to the data points of interest, and the proper length of 
time for completion of data abstraction on a single patient. The pre-test results will be reviewed 
by CHSS with Pfizer. No data from the pre-testing phase will be used in the current study. 
Additionally, prior to data collection (during the field test and actual study launch), CHSS will 
complete the previously described user acceptance testing (UAT), inputting various clinical 
scenarios and identifying function edit checks and checks that are required to be made 
manually post-data collection. Results of the UAT will be included in the data QC log. Any 
changes made to the CRF document as a result of the pre-test will require the resubmission of 
the CRF and study protocol to the IRB.
Participating providers are informed in their contractual agreement that follow-up with CHSS 
may be required and are contacted for query resolution and/or data validation as needed. For 
medical queries and random data validation, providers will be asked to create a 4-digit unique 
identifier for each patient, which will be transmitted to Cardinal Health and used for identifying 
the patient record for data validation. Data will be reviewed by a licensed healthcare 
professional (HCP) employee of Cardinal Health to identify medical queries. Data will be 
further reviewed by an analyst and scientist to check for face validity of aggregate results (e.g., 
statistical outliers; eCRF completion in an unexpectedly short time; treatment regimens 
unknown to be used for the disease under study; individual provider responses compared with 
aggregate responses; laboratory, pathology, and radiology results inconsistent with known 
clinical parameters; other clinical data inconsistent with known standards and outcomes; and 
distribution and content of key variables needed for analysis). Issues flagged for potential data 
validation will be resolved with the providers directly on a case-by-case basis. Any eCRF 
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flagged during QC will be reviewed by the team to determine the level of follow-up needed. 
Individual eCRFs that cannot be validated will be removed from the dataset, and the respective
provider will not be compensated for the eCRF that is removed.
Random data validation occurs by selecting a random eCRF from each provider submitting a 
patient. Providers subjected to random validation are asked to complete a 3 data point-
validation exercise for the patient, whereby the provider is given the unique patient identifier 
but no other information. The provider is then asked to re-enter the data elements. The 3 data 
points may include: month/year of treatment initiation, stage at diagnosis, and date of treatment 
discontinuation (or date of last treatment/prescription if patient is still on therapy). Providers 
who had been previously verified by CHSS will not be subject to random validation. A verified 
provider is any physician abstractor who has completed at least 2 of the following: (1) 
completed and acknowledged CHSS web-based chart data abstraction training in the past 2 
years, (2) participated in a chart review pre-test with screen sharing, (3) participated in two 
previous chart review studies in the past 2 years and accurately validated data, and (4) 
completed a phone interview with the CHSS team for data validation. Despite a provider 
having been verified, however, he or she will still be required to answer questions regarding 
patients with data flagged by the research operations or research analytics teams. A provider 
who fails to validate all data points for a selected patient will be required to submit to further 
clinical data review. No resampling to replace any excluded eCRF will be conducted. 
After completion of QC/QA reviews and for all completed eCRFs, the study database will be
locked, and all data will be downloaded and stored on a secured server housed within the 
Cardinal Health Information Technology infrastructure. Analyses for all research objectives 
will be performed at that time.
9.9. Strengths and limitations of the research methods
9.9.1. Strengths
The extensive CHSS network of oncologists/hematologists is geographically diverse, 
EHR/GPO-agnostic, and inclusive of multiple settings of community oncology care, thus 
making the survey results representative of the US oncology provider pool and patient 
population. Retrospective medical chart review provides in-depth knowledge of biomarker 
testing, diagnostic testing, treatment patterns, clinical outcomes, and rationale for treatment 
decisions using an efficient, reliable, and verifiable method. Chart review studies are therefore 
well suited for oncology as these clinical parameters are important to assess the patient journey, 
especially with the current focus on targeted, precision, and personalized medicine. Further, 
data are abstracted by providers for patients under their care, ensuring high data quality as the 
abstractor does not have to make assumptions about data elements. The majority of physicians 
invited to participate in this study have undergone various training sessions with CHSS staff 
related to abstraction of data from patients’ medical charts and completion of eCRFs and are 
well versed with the chart abstraction process. Finally, many of the data elements of interest, 
including biomarker results, are often not available in structured or unstructured EHR fields, 
and physician-abstracted chart review allows for collection of these difficult-to-retrieve 
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9.9.2. Limitations
As is a limitation of any observational research study, not all patient characteristics will be 
included in the data collection (e.g., income and other variables that may influence physician 
prescribing behavior or treatment decisions), thereby allowing for potential unmeasured and 
residual confounding that cannot be accounted for in descriptive, univariate, multivariate, or 
subgroup analyses. 
CHSS does not, and cannot, conduct source document verification. CHSS requires that all 
physicians submit to at least 1 random data validation check during the study whereby they are 
asked to re-enter 3 data points regarding a patient. Physicians failing to correctly re-enter data 
are subject to further review, and at the discretion of CHSS, may have all patient records 
submitted removed from the analytic dataset.
This study employs purposive sampling that selects physicians and patients based on pre-
specified selection criteria and hence, this may not be representative of all patients within the 
cohorts of interest or representative of all physicians treating these patients. Physicians invited 
to participate in this study will represent a subset of OPEN physicians. Importantly, treatment 
patterns reflected in the study will represent only the practices of physicians who have 
volunteered to participate, and may vary from non-responding physicians (i.e., those who 
refused study participation or who did not respond to the screening invitation). No data will be 
available to describe non-participating providers or non-selected patients. CHSS cannot verify 
that all patients who meet the study eligibility criteria are included in the final dataset, and 
participating providers will initially be limited to submitting a maximum of 10 eCRFs in an 
aim to minimize provider bias (this maximum number of eCRFs may be increased if necessary, 
to aid in recruitment following prior approval from Pfizer). However, based on estimates of 
eligible patients reported by physicians who participated in the short chart review study, we 
expect the majority of providers to manage 10 or fewer eligible patients. Although bias related 
to selection of patient subsets within practices may occur, physicians will be instructed to 
identify all eligible patients and to select patients chronologically starting with eligible patients 
who initiated talazoparib the earliest within the study index period.
Additionally, this study may be subject to bias due to missing data. Although physicians will 
be required to record all relevant patient experiences in the medical charts, there may be 
undercounting of events that are unknown to them due to having occurred outside the 
office/clinical setting. Further, loss to follow-up may occur if patients transfer care to other 
providers or clinics. As such, treatments, visits, and outcomes occurring after the date of last 
visit may be missing. Further, this study involves retrospective extraction of data from medical 
records. Thus, the accuracy and completeness of the data collected are limited by the quality 
and nature of data available in the EHR and abstracted into the eCRF. Further, loss to follow-
up may occur if patients transfer care to other providers or clinics. As such, treatments, visits, 
and outcomes occurring after the date of last visit may be missing. Additionally, the follow-up 
period may not be long enough to observe all disease progression events during therapy. 
 
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Finally, findings from this study may be impacted by a lack of uniform assessment criteria for 
certain variables such as disease response.
9.10. Other aspects
Not applicable.
10. PROTECTION OF HUMAN SUBJECTS
At all times, patient PHI is kept confidential in accordance with HIPAA. The eCRF will not 
capture any data related to the patient’s name, full date of birth, social security number, health 
insurance plan number, medical record number, or other such PHI. However, date of disease 
diagnosis, date(s) of treatment(s) administered (including dates of dose changes), date of 
development of health states of interest (e.g., disease progression), and dates of death (if 
available) will be collected. These items are considered PHI under HIPAA. At no time will 
Pfizer be provided with PHI in the form of a dataset or otherwise; all study results will be 
reported in aggregate. Additionally, exact dates (e.g., of dose changes) will not be reported 
during analysis but will be used to calculate intervals of time between relevant anchor date and 
end dates of interest.
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, 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. 

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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.
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.
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 AEs 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 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 eCRF 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.

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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 (e.g., 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.
All research staff members must complete the following Pfizer training requirements:   

“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
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.  
13. REFERENCES
1.
ACS. American Cancer Society Cancer Statistics Center: Breast Cancer. 2021; 
https://cancerstatisticscenter.cancer.org/?_ga=2.72864211.1312339105.1586458273-
885389106.1584627111#!/cancer-site/Breast.
2.
Liang Y, Zhang H, Song X, Yang Q. Metastatic heterogeneity of breast cancer: 
Molecular mechanism and potential therapeutic targets. Semin Cancer Biol. 
2020;60:14-27.

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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):384-391.
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-
121.
7.
Patel M, Nowsheen S, Maraboyina S, Xia F. 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, Clarke PA, Workman P, Al-Lazikani B. 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):8297-8308.
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-
1091.
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. US. Food and Drug Administration: FDA approves talazoparib for gBRCAm 
HER2-negative 
locally 
advanced 
or 
metastatic 
breast 
cancer. 
2018; 
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):753-763.
14.
Zimmer AS, Gillard M, Lipkowitz S, Lee J-M. Update on PARP Inhibitors in Breast 
Cancer. Current Treatment Options in Oncology. 2018;19(5):21.
14. LIST OF TABLES 
None

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15. LIST OF FIGURES
Figure 1. Study period
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS
None.
ANNEX 2. ENCEPP CHECKLIST FOR STUDY PROTOCOLS
Not applicable.
ANNEX 3. ADDITIONAL INFORMATION
Not applicable.