A Retrospective Medical Record Review of First-Line Sunitinib Administration Schedules and Outcomes Among Patients With Metastatic Renal Cell Carcinoma in Latin America
Conditions: Metastatic Renal Cell Carcinoma ( mRCC)
Sponsor: Pfizer

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NONINTERVENTIONAL (NI) STUDY PROTOCOL
Title
A Retrospective Medical Record Review of First-Line Sunitinib 
Administration Schedules and Outcomes Among Patients with 
Metastatic Renal Cell Carcinoma in Latin America 
Protocol 
number
A6181231
Protocol version 
identifier
V1
Date
13 June 2019
Research 
question and 
objectives
To describe real-world demographic and clinical characteristics, 
treatment characteristics, and clinical outcomes (eg, adverse events, 
progression-free survival) among patients in Latin America who 
were treated with first-line sunitinib for metastatic renal cell 
carcinoma and switched from the 4/2 to 2/1 administration 
schedule. In Brazil, an additional sample of patients who initiated 
sunitinib on the 2/1 schedule will be analyzed.
Authors
Pfizer Inc:
, PharmD, MSc
, MSPH
, MS
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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TABLE OF CONTENTS
1. LIST OF ABBREVIATIONS................................................................................................4
2. RESPONSIBLE PARTIES....................................................................................................6
3. ABSTRACT...........................................................................................................................8
4. AMENDMENTS AND UPDATES.....................................................................................10
5. MILESTONES.....................................................................................................................11
6. RATIONALE AND BACKGROUND................................................................................12
7. RESEARCH QUESTION AND OBJECTIVES .................................................................14
8. RESEARCH METHODS ....................................................................................................14
8.1. Study Design ...........................................................................................................16
8.2. Setting......................................................................................................................17
8.2.1. Patient Inclusion Criteria............................................................................17
8.2.2. Exclusion Criteria.......................................................................................18
8.3. Variables..................................................................................................................18
8.3.1. Patient Characteristics ................................................................................18
8.3.2. Baseline Clinical Characteristics................................................................18
8.3.3. Treatment Patterns......................................................................................19
8.3.4. Treatment-related Outcomes ......................................................................20
8.4. Data Sources and Data Collection Method .............................................................20
8.5. Study Size................................................................................................................21
8.6. Data Management ...................................................................................................21
8.6.1. Documentation of SAS Programming........................................................22
8.6.2. Validation of SAS Programs ......................................................................22
8.6.3. Log Review.................................................................................................22
8.6.4. Review of Data Listings and Tables of Summary Statistics.......................23
8.6.5. Independent Programming..........................................................................23
8.6.6. Validation Documentation..........................................................................23
8.6.7. Case Report Forms (CRFs)/Data Collection Tools (DCTs)/Electronic 
Data Record .....................................................................................................23
8.6.8. Database Storage and Retention.................................................................24
8.7. Data Analysis ..........................................................................................................24

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8.8. Quality Control........................................................................................................25
8.9. Limitations ..............................................................................................................26
8.10. Other Aspects ........................................................................................................26
9. PROTECTION OF HUMAN SUBJECTS ..........................................................................27
9.1. Patient Information..................................................................................................27
9.2. Patient Consent........................................................................................................28
9.3. Participation Withdrawal.........................................................................................28
9.4. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ..............28
9.5. Ethical Conduct of the Study ..................................................................................28
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS ......................................................................................................................30
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS........32
12. REFERENCES ..................................................................................................................33
13. LIST OF TABLES.............................................................................................................34
14. LIST OF FIGURES ...........................................................................................................34

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1. LIST OF ABBREVIATIONS
Abbreviation
Definition
AE
adverse event
AEM
adverse event monitoring
ANMAT
Administración Nacional de Medicamentos, 
Alimentos y Tecnología Médica
ANVISA
Agência Nacional de Vigilância Sanitária
CEISH
Ethics Committee of Human Research
CENDEISSS
Centro de Desarrollo Estratégico e Información en 
Salud y Seguridad Social
CI
confidence interval
COFEPRIS
Comisión Federal para la Protección contra Riesgos 
Sanitarios
COMBIOETICA
La Comisión Nacional de Bioética
CONEP
Comissão Nacional de Ética em Pesquisa
CONIS
Consejo Nacional de Investigación en Salud
CRF
case report form
DCF
data collection form
DCT
data collection tool
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
ERB
ethical review board
GPP
Good Pharmacoepidemiology Practices
HR
hazard ratio
IEC
independent ethics committee
IMDC
International Metastatic Renal Cell Carcinoma 
Database Consortium
INVIMA
Instituto Nacional de Vigilância de Medicamentos y 
Alimentos
IRB
institutional review board
ISPE
International Society for Pharmacoepidemiology
ISPOR
International Society for Pharmacoeconomics and 
Outcomes Research
MSKCC
Memorial Sloan Kettering Cancer Center
NIS
noninterventional study
OQA
Office of Quality Assurance
PFS
progression-free survival
PI
principal investigator
Q
quarter
RAINBOW
RAnibizumab Compared With Laser Therapy for the 
Treatment of INfants BOrn Prematurely With 
Retinopathy of Prematurity

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Abbreviation
Definition
RCC
renal cell carcinoma
RECIST
Response Evaluation Criteria in Solid Tumors
SAS
Statistical Analysis Software
STAR-TOR
Registry For Temsirolimus, Sunitinib, And Axitinib 
Treated Patients With Metastatic Renal Cell 
Carcinoma (mRCC), Mantle Cell Lymphoma (MCL), 
And Gastro-Intestinal Stroma Tumor (GIST)
TBD
to be determined
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2. RESPONSIBLE PARTIES
Principal Investigator(s) of the Protocol
Name
Job Title
Affiliation
Contact
, 
PharmD, MSc
 
Pfizer Inc.
 
, 
MD
 
 
Pfizer Inc.
 
, 
MSPH
 
 
, MS
 
 
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Country Coordinating Medical Leads/Investigators
Name
Job Title
Affiliation
Address
Pfizer Inc.
 
 
 
Pfizer Inc.
 
Pfizer Inc.
 
Pfizer Inc.
 
Pfizer Inc.
 
 
 
Pfizer Inc.
 
 
 
Pfizer Inc.
 
 
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3. ABSTRACT
A Retrospective Medical Record Review of First-Line Sunitinib Administration Schedules 
and Outcomes Amogn Patients with Metastatic Renal Cell Carcinoma in Latin America
Version 1
Background: Over the past decade, targeted therapies have yielded significant improvement 
in the clinical outcomes of patients with metastatic renal cell carcinoma (RCC), leading to 
international guidelines for standard first-line treatment with sunitinib, bevacizumab + 
interferon, or pazopanib for patients with good or intermediate prognoses.1 The standard 
administration schedule for sunitinib as first-line treatment for metastatic RCC is 50 mg per 
day for 4 weeks followed by 2 weeks off (ie, a 4/2 schedule).  However, recent studies 
suggest that a schedule modified to 2 weeks of sunitinib followed by 1 week off (ie, a 2/1 
schedule) improves tolerability with comparable outcomes.2-5 A change to the schedule may 
result in fewer Grade 3 or Grade 4 toxicities and increased treatment duration.5-9
Rationale: Despite the potential benefit from a modified treatment schedule evidenced in 
several studies among patients in the United States and Europe, real-world clinical outcomes 
among patients who have switched from the 4/2 to the 2/1 schedule for metastatic RCC in 
Latin America are unexplored.  The current study will provide a description of demographic 
and clinical characteristics, sunitinib treatment patterns, and associated adverse events (AEs) 
and outcomes among adult patients in Latin America who were diagnosed with metastatic RCC 
and who received first-line sunitinib on the 4/2 schedule and then switched to the 2/1 schedule.
In Brazil, feasibility assessments indicate many physicians start patients on the 2/1 schedule 
upon initiation of sunitinib for metastatic RCC. To reflect the patient population in Brazil, a 
second sample of patients who initiated first-line sunitinib on the 2/1 schedule will be collected 
and analyzed separately.
Primary Objectives:
1. Describe demographic and clinical characteristics of patients in Latin America 
diagnosed with metastatic RCC who received first-line sunitinib and switched from 
the 4/2 to the 2/1 schedule.
2. Characterize detailed first-line sunitinib treatment patterns, including dose, schedule, 
total duration of sunitinib treatment, duration on the 4/2 schedule, duration on the 
2/1 schedule, reasons for stopping treatment lines, and supportive care.
Secondary Objectives:
1. Explore clinical outcomes after switching to the 2/1 schedule, including response to 
treatment, AEs, progression-free survival (PFS), and overall survival.
2. Describe demographic, clinical and treatment characteristics (eg, duration of 
treatment, reasons for stopping treatment), and clinical outcomes (eg, treatment 
response, AEs, PFS, and overall survival) among patients in Brazil who initiated 
first-line sunitinib treatment for metastatic RCC on the 2/1 schedule.

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Study Design: Noninterventional, retrospective medical record review of patients with 
metastatic RCC who received first-line treatment with sunitinib and switched from the 4/2 to 
2/1 administration schedule. A second sample of patients who initiated first-line treatment 
with sunitinb on the 2/1 schedule in Brazil will be collected and analyzed separately.
Population: Patients diagnosed with metastatic RCC with clear cell histology who switched 
from a 4/2 schedule to a 2/1 schedule of sunitinib in first-line metastatic treatment between 
January 1, 2014 and June 30, 2018.  Patients must be aged 18 years or older at the time of the 
switch.  The final dates defining this selection period will be dependent on country-specific 
ethics and reporting requirements.  A second sample of adults who initiated first-line 
treatment with sunitinb on the 2/1 between January 1, 2014 and June 30, 2018 in Brazil will 
be collected and analyzed separately.
Variables: Patient characteristics, clinical characteristics, first-line treatment patterns, 
treatment-related outcomes, AEs, and survival.
Data Sources: Information will be abstracted from patients’ medical records and compiled 
into an anonymized analytic database.  All abstracted information will be retrospective.
Study Size: Data will be abstracted from a target of at least 150 medical records of patients 
treated at various sites across 7 Latin American countries.
Data Analysis: Analyses will include a descriptive summary of patient characteristics, 
first-line treatment patterns (eg, time to switch from 4/2 to 2/1; 4/2, 4/1, and total treatment 
durations), first-line disease progression from the start of 4/2 and the start of 2/1 schedules,
AEs, and survival from the start of 4/2 and the start of 2/1 schedules.  Time-to-event 
outcomes (ie, overall survival, treatment duration, PFS) will be described using the 
Kaplan-Meier method.  Patients who initiated treatment on the 2/1 schedule will be analyzed 
separately from patients who switched from the 4/2 to 2/1 schedule.
Milestones: Key milestones include finalization of the protocol and case report form 
(quarter [Q]2 2019), initiation of site feasibility assessments (Q1 2019), initiation of the
ethics review process (Q2 2019), start of data collection (to be determined; following 
completion of ethics review on a site-by-site basis), final interim analysis (Q3/Q4 2019), and 
final analytic results and final study report (to be determined based on site contracting
timelines).

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4. AMENDMENTS AND UPDATES
None.

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5. MILESTONES
Milestone
Planned date
Initiate feasibility assessment with sites after sites 
complete the confidentiality agreement with 
Q1 2019
Finalize study materials
Q2 2019
Initiate ethics review process after 
 
contracts with a participating site
Q2 2019
Start of data collection
TBD (following completion of 
ethics review on a site-by-site 
basis)
Final interim analysis
Q3/Q4 2019
Final analytic results
TBD (based on site contracting 
timelines) 
Final study report
TBD (based on site contracting 
timelines)
TBD = to be determined; Q = quarter; 
.
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6. RATIONALE AND BACKGROUND
Worldwide, kidney cancer is the ninth most commonly diagnosed cancer, with approximately 
338,000 new cases diagnosed in 2012.10 In Latin America and the Caribbean, the incidence 
of kidney cancer is 2.5 and 4.7 per 100,000 females and males, respectively, which is slightly 
lower than the global incidence.11 However, regional cancer registry data indicate a greater 
incidence per 100,000 in many Central and South American countries including Uruguay 
(females, 5.7; males, 13.4), Chile (females, 5.6; males, 10.4), Argentina (females, 4.5; males, 
10.4), and Brazil (females, 3.0; males, 5.8).12 Although kidney cancer also refers to cancers 
affecting the renal pelvis and ureter, which are typically transitional (urothelial) cell 
carcinomas, renal cell carcinoma (RCC) makes up approximately 80% of all kidney cancers.1
RCC is a highly vascularized solid tumor and angiogenesis is linked to proliferation and 
propensity for metastasis.13-15 Over the past decade, targeted therapies, specifically 
angiogenesis inhibitors, have yielded significant improvement in the clinical outcomes of 
patients with metastatic RCC, leading to international guidelines for standard first-line 
treatment with sunitinib, bevacizumab + interferon, or pazopanib for patients with good or 
intermediate prognoses.1
The standard administration schedule for sunitinib as first-line treatment for metastatic RCC 
is 50 mg per day (oral dose) for 4 weeks followed by 2 weeks off (ie, a 4/2 schedule).  In this 
scheme, sunitinib demonstrated a greater median overall survival over interferon alpha 
(26.4 vs. 21.8 months, respectively; hazard ratio [HR] = 0.821; 95% confidence interval [CI], 
0.673 to 1.001; P = 0.051).16 Median progression-free survival (PFS) was significantly 
longer in the sunitinib group (11 months) compared with the interferon alpha group 
(5 months) (P <0.001).  Yet, sunitinib-related Grade 3 adverse events (AEs) such as 
hypertension (12%), fatigue (11%), diarrhea (9%), and hand-foot syndrome (9%) were 
observed.  The dose intensity of sunitinib must be maintained for disease control.  Higher 
exposure has been linked to better treatment response, extended time to progression, and 
overall survival.17 However, treatment-related adverse events can lead to reductions in dose 
or dose interruptions, which in turn may lead to impaired quality of life and poorer outcomes 
as dosing is not maintainted.17,18 The optimal treatment approach for maintaining sunitinib 
dosing while mitigating adverse events is unknown.2
Recent studies suggest that a schedule modified to 2 weeks of sunitinib followed by 1 week off 
(ie, a 2/1 schedule) improves tolerability with comparable outcomes.2-5 A change to the 
schedule may result in fewer Grade 3 or Grade 4 toxicities and increased treatment duration.5-8  
In the RAINBOW study, researchers evaluated safety and efficacy of the 2/1 schedule among 
patients receiving sunitinib for metastatic RCC in multiple centers in Europe.  Findings 
indicated patients who switched from the 4/2 to the 2/1 schedule experienced a favorable safety 
profile compared to the prevalence and frequency of adverse events occurring during the initial 
4/2 schedule.7 A single site study of patients receiving first-line sunitinib also observed fewer 
toxicities among patients on the 2/1 schedule compared to those on the 4/2 schedule and 
comparable objective response rates and overall survival between the 2 groups.3 The 
STAR-TOR study, a large German registry containing patients who receive sunitinib for 

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metastatic RCC (among other patients), reported similar adverse event mitigation with the 
2/1 schedule and treatment duration more than three times longer than those who received the 
4/2 schedule.6 Longer duration translates to longer dose maintenance, which improves clinical 
outcomes.
Despite the potential benefit from a modified treatment schedule evidenced in studies among 
patients in the United States and Europe, real-world clinical outcomes among patients 
receiving the 2/1 schedule for metastatic RCC in Latin America are unexplored.5-9  Further 
research on current, real-world clinical outcomes in this population may assist in providing 
additional context on the types of patients who may benefit from this alternative schedule.
The aim of the present study is to describe clinical characteristics, treatment patterns, and 
clinical outcomes (eg, PFS, change in prevalence of AEs) of adult patients with metastatic
RCC in Latin America who received first-line sunitinib on the 4/2 schedule and then 
switched to the 2/1 schedule.  In Brazil, feasibility assessments indicate many physicians start 
patients on the 2/1 schedule upon initiation of sunitinib for metastatic RCC. To reflect the 
patient population in Brazil, a second sample of patients who initiated first-line sunitinib on the 
2/1 schedule will be collected and analyzed separately. As patient characteristics, prescribing 
patterns, health care systems, and access to care in community practice settings differ from 
highly controlled clinical trial environments, clinical outcomes (eg, treatment response, PFS, 
overall survival) in real-world patient populations may vary from published trials.  As current 
research on health outcomes among patients who received sunitinib on a 2/1 schedule for 
metastatic RCC in these countries is absent, there is a lack in understanding as to whether the 
alternative treatment schedule is safe and effective in patients in Latin America.
Results from this study may aid in the following:

Understanding characteristics of patients who switched from a 4/2 to a 2/1 sunitinib 
schedule or initiated the 2/1 schedule in Brazil, and the resulting clinical outcomes in 
the real-world setting.

Describing the occurrence of AEs on the 4/2 and 2/1 schedules.

Providing real-world, baseline measures of contemporary prescribing patterns and 
health outcomes to which future innovations in therapy could be compared.

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7. RESEARCH QUESTION AND OBJECTIVES
This study consists of compiling and analyzing recent data from a customized retrospective 
medical record review conducted in 7 countries (Argentina, Brazil, Colombia, Costa Rica, 
Ecuador, Mexico, and Peru) to assess the following primary objectives:
•
Describe demographic and clinical characteristics of patients in Latin America 
diagnosed with metastatic RCC who received first-line sunitinib and switched from 
the 4/2 to the 2/1 schedule.
•
Characterize detailed first-line sunitinib treatment patterns, including dose, schedule, 
total duration of sunitinib treatment, duration on the 4/2 schedule, duration on the 
2/1 schedule, reasons for stopping treatment lines, and supportive care.
The secondary objectives of the study will include an exploration of clinical outcomes 
(ie, response to treatment, AEs, PFS, and overall survival) after switching to the 
2/1 schedule.  Switching to the 2/1 schedule is a relatively new occurrence in the studied 
countries, resulting in limited available follow-up time to observe clinical outcomes among 
patients who switched to the alternative schedule. Furthermore, this study relies on a 
convenience sample of sites treating patients at a select number of treatment centers, will 
provide only descriptive information on observed events, and is designed to generate, not 
test, hypotheses. In Brazil, early feasibility results suggest physicians frequently prescribe 
sunitinib on the 2/1 schedule at first-line initiation; therefore, secondary objectives will also 
include a descriptive exploration of demographic, clinical and treatment characteristics 
(eg, duration of treatment, reasons for stopping treatment), and clnical outcomes (eg, 
treatment response, AEs, PFS, and overall survival) among patients initiating first-line 
sunitinib on the 2/1 schedule. It is anticipated this sample will be relatively small.  
Secondary objectives will be assessed with known limitations concerning data availability 
and generalizability of the findings.
8. RESEARCH METHODS
To achieve the study objectives described in Section 7 , 
, a 
research consultancy specializing in conducting multinational real-world health economic 
and outcomes studies, will analyze retrospective medical record data from 150 patients who 
received care at treatment centers across 7 Latin American countries.  Prior to initiation of 
data collection activities, 
, in consultation with Pfizer Inc. (Pfizer), will develop a 
customized case report form (CRF) to capture detailed data on demographics, clinical 
characteristics, treatment patterns, AEs, and health outcomes from eligible patients’ medical 
records.  The length of the CRF will be consistent with an abstraction time burden of 
approximately 30 to 45 minutes.  After selection of potential sites by Pfizer, 
will 
work with the sites to assess feasibility of the site’s participation by using a site information 
form.  If the study is determined to be feasible at a specific site, the principal investigator (PI) 
and their designated research team at the participating site will obtain the necessary ethics 
approvals for conducting this study.  In countries where national ethics activities are 
required, a lead site in the relevant country will be selected to support the national 
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submission.  Specific responsibilities to be conducted and coordinated by Pfizer, 
, 
and individual sites during the site identification, feasibility assessment, contracting process, 
and data collection are shown in Figure 1.
Following receipt of the required ethics approvals, the site PI and/or designated research 
team will be provided a link(s) to the secure electronic CRF (eCRF) to enter the abstracted 
data electronically.  The PI may personally abstract data and/or designate their research team
to abstract data.  Once a potential medical record is identified, the abstractor will answer 
multiple screening questions in the eCRF to confirm the selected medical record is eligible 
for inclusion.  Next, the abstractor will complete the eCRF by retrospectively reviewing all 
available data in the patient’s medical record.
During the data collection phase, 
 will monitor recruitment and data collection 
activities.  Upon completion of data collection, 
 will perform the analyses required to 
address Pfizer’s study objectives.  One interim analysis on partial data may be conducted 
upon Pfizer’s request.  Finally, 
, in consultation with Pfizer, will develop a study 
report presenting the study methods, the CRF, the study results in the form of relevant tables 
and figures, and an interpretation of the results.
Figure 1.
Site Selection, Feasibility Assessment, Contracting, and Data Collection 
Responsibilities
AE = adverse event; CDA = confidential disclosure agreement; CRF = case report form; PI = principal 
investigator; 
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8.1. Study Design
This study is a retrospective, observational medical record review of adult patients with 
metastatic RCC.  A sample of 150 records of patients who meet the eligibility criteria 
described in Section 8.2.1 will be targeted.  Data describing patient and clinical 
characteristics, first-line treatment patterns, AEs, and clinical outcomes will be abstracted 
directly by the PI and/or their designated research team.  This study is descriptive, with the 
primary goal of retrospectively summarizing existing sunitinib treatment patterns and patient 
outcomes.  As the data collected will be retrospective, the conduct of this study will in no 
way influence prescribed treatment.  Figure 2 presents a graphical summary of the study 
design for patients who switched from the 4/2 to 2/1 schedule.  Figure 3 displays a summary 
of the study design for the sample of patients in Brazil who initiated first-line sunitinib on the 
2/1 schedule. 
The primary measures of interest are described in Section 8.3.
Figure 2.
Study Design: First-Line Switch From 4/2 to 2/1 Sunitinib
RCC = renal cell carcinoma.
Note: The end of study follow-up may be contingent on country-specific or site-specific ethics requirements, for 
example, the last date of available data on the date of ethics approval at a given site.  Patients may have a gap 
between stopping the 4/2 schedule and starting the 2/1 schedule.

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Figure 3.
Study Design: Initiated First-Line 2/1 Sunitinib (Brazil Only)
RCC = renal cell carcinoma.
Note: The end of study follow-up may be contingent on country-specific or site-specific ethics requirements, for 
example, the last date of available data on the date of ethics approval at a given site.  
8.2. Setting
Data for this study will be abstracted from the medical records of patients treated for 
metastatic RCC at approximately 17 treatment centers (ie, sites) in 7 countries: Argentina, 
Brazil, Colombia, Costa Rica, Ecuador, Mexico, and Peru.
8.2.1. Patient Inclusion Criteria
1. Diagnosed with metastatic RCC with clear cell histology:
a.
The patient may have been initially diagnosed with Stage IV or initially diagnosed 
at an earlier stage and progressed to having disease at distant sites (ie, metastatic 
disease).
2. Initiated first-line treatment for metastatic RCC with sunitinib on the 4/2 schedule (all 
countries) or initiated first-line treatment for metastatic RCC with sunitinib on the 
2/1 schedule (Brazil only).
3. Switched to the 2/1 schedule (all countries) or initiated the 2/1 schedule (Brazil only) 
during the first treatment line between January 1, 2014, and June 30, 2018:
a.
The final dates defining this selection period will be dependent on 
country-specific ethics and reporting requirements.
4. Aged 18 years or older at the time of the switch to the 2/1 schedule (all countries) or 
initiation of the 2/1 schedule (Brazil only).

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8.2.2. Exclusion Criteria
1. Evidence of other malignant neoplasms (except nonmelanoma skin cancer or 
carcinoma in situ) within 5 years before switching to the sunitinib 2/1 schedule (all 
countries) or initiation of the 2/1 schedule (Brazil only).
8.3. Variables
All measures/variables will be gathered from existing medical records using the eCRF.  In 
the following sections, we describe the key analysis variables and study measures that will be 
gathered directly through the eCRF or constructed during analysis.
8.3.1. Patient Characteristics
Demographic characteristics available in patients’ medical records will be documented, 
including, but not limited to, the following (when available):

Sex;

Year of birth;

Primary health insurance type (eg, supplemental private insurance, uninsured), if 
relevant;

Comorbidities (eg, hypertension, diabetes);

Height;

Weight;

Body mass index.
8.3.2. Baseline Clinical Characteristics
A number of clinical characteristics related to the initial RCC diagnosis and diagnosis of 
metastatic RCC will be collected.  These characteristics may include, but are not limited to,
the following (when available):

Dates of diagnosis of initial (if first diagnosed at an earlier stage) and metastatic
RCC;

Stage of RCC at the time of initial diagnosis;

Tumor grade at the time of initial diagnosis;

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
Risk group at the time of initial diagnosis (eg, Memorial Sloan Kettering Cancer 
Center [MSKCC], International Metastatic Renal Cell Carcinoma Database 
Consortium [IMDC]);

Site(s) of distant metastases at the time of initiation of first-line treatment with 
sunitinib and at the switch;

Performance status (eg, Eastern Cooperative Oncology Group [ECOG], Karnofsky
Performance Status Scale) at the time of initiation of first-line treatment with 
sunitinib and at the switch.
8.3.3. Treatment Patterns
Measures related to the treatment of RCC before (if applicable) and after diagnosis of 
metastatic RCC will be gathered.  Figure 2 graphically depicts the time periods during which 
treatment patterns will be assessed for each sample.  Treatment measures may include the 
following:

Receipt of broad categories of treatment approaches, including neoadjuvant 
treatment(s), surgery, and adjuvant therapy before the diagnosis of metastatic RCC:

Date of receipt of last cancer-direct treatment before the diagnosis of metastatic 
RCC.

Total number of systemic lines of treatment after the diagnosis of metastatic RCC:

Start and stop dates of each treatment line (duration of each treatment line will be 
calculated).

Specific details regarding first-line treatment with sunitinib after the diagnosis of 
metastatic RCC include the following (where relevant to the specific sample):

Start and stop dates of the 4/2 schedule (duration of 4/2 treatment);

Date of switch to or initiation of the 2/1 schedule and stop date (duration of 
2/1 treatment);

Time between stopping the 4/2 schedule and initiating the 2/1 schedule;

Reason for switch to 2/1 schedule;

Date of subsequent changes in schedule, if any

Reason for subsequent changes in schedule, if any

Initial and subsequent daily dose(s) of sunitinib on the 4/2 and 2/1 schedules:

Date(s) of dose change(s), if applicable;

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
Reason for change(s) in dose, if applicable.

Reason for stopping treatment with sunitinib (eg, AE, progressive disease);

Best clinician assessed response to treatment with sunitinib on the 4/2 schedule 
and best response on the 2/1 schedule.

Receipt of broad categories of supportive care elements (medications and procedures) 
such as nutritional supplements, pain medications, antibiotics, antifungals, iron 
supplements, antiemetics/antinauseants, antidiarrheals, antivirals, radiation therapy, 
bone-targeting agents (eg, bisphosphonates, denosumab), erythropoiesis-stimulating 
agents, granulocyte-colony stimulating factors, folic acid, red blood cell transfusion,
and platelet transfusion during the first line of treatment with sunitinib.
8.3.4. Treatment-related Outcomes
Treatment-related AEs (eg, hypertension, neutropenia, thrombocytopenia, fatigue, stomatitis) 
will be documented for the duration of first-line treatment with sunitinib.  Frequency of 
toxicity evaluation (eg, every 6 weeks) and the method of evaluation (eg, radiological 
evaluations by computed tomography, magnetic resonance imaging with measurable lesions 
via Response Evaluation Criteria in Solid Tumors [RECIST]) will also be documented.
Dates of progression and death (ie, whether the patient died during the follow-up period and 
whether the death was related to RCC) will be documented.  Disease progression and 
survival estimates will be derived from these measures and calculated from the date of 
diagnosis of metastatic RCC, the start of first-line treatment line with 4/2 or 2/1 sunitinib, 
and the time of switch to the 2/1 schedule (among those who initiated on the 4/2 schedule).  
Survival estimates will include, but are not limited to, the following:

Overall survival;

PFS;

Time to second-line initiation.
8.4. Data Sources and Data Collection Method
Data will be abstracted from the medical records of patients at various treatment centers in 
the selected countries.  This study is retrospective; therefore, the collection of data will in no 
way influence prescribing patterns or treatment decisions.
Medical record abstractions provide a unique opportunity to collect and analyze real-world 
data outside the highly controlled setting of clinical trials.  Generally, medical record 
abstraction enables collection of detailed information on patient demographic and clinical 
characteristics, treatment patterns, and health outcomes that may otherwise be unavailable in 
a standardized manner.  The use of medical record abstraction allows for the development of 
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While ethics activities at sites are ongoing, the CRF will be programmed into a web-based 
eCRF.  Following ethics approval and finalization of the eCRF, 
will send secure 
links of the eCRF to the PI or the designated study coordinator of each site.  The PI and/or 
their designated research team will screen their patients’ records to identify eligible patient
records.  Once a potential medical record is identified, the PI and/or their research team will 
answer multiple screening questions in the eCRF to confirm the selected medical record is 
eligible for inclusion.  After the medical record is determined to be eligible, the PI and/or 
their research team will complete the eCRF form by retrospectively reviewing all available 
data in the medical record.  See Section 8.9 for a detailed review of the limitations of this 
study type.  It is anticipated that it will take an abstractor approximately 30 to 45 minutes to 
complete the CRF for each patient record.
8.5. Study Size
A convenience sample of at least 150 medical record abstractions will be targeted across all 
sites and 7 Latin American countries.  As this study is descriptive in nature, no formal power 
calculations were conducted to determine the sample size for this study.  This study does not 
involve hypothesis testing (via statistical testing) and is primarily being conducted to 
understand clinical characteristics, sunitinib treatment patterns, and health outcomes.
It is anticipated that all participating sites will provide data for all eligible patients.  If any
site estimates a greater number of eligible patients than needed to meet the total study sample 
size in the respective country, that site will be required to select a quasi-random sample of 
eligible patients for the study.  This process will entail selection of medical records for 
patients whose last names begin with a randomly generated letter between A and Z, provided 
to the abstractor during data collection.  For example, if “M” is the randomly generated first 
letter and if the abstractor does not have any patients who meet the study criteria and whose 
last name begins with “M,” then they will select a patient whose last name begins with the 
next letter in alphabetical order (in this example, “N”).  Due to variations in the distribution 
of first letters among last names, patients may not have an equal probability of inclusion in 
the study.
The PIs will be responsible for meeting sample size expectations at their respective sites.  In 
the event that sample sizes are not met with the selected sites, other sites with additional 
eligible patients may be asked to provide data for additional patients or new sites may be 
recruited.  The anticipated sample size in each country will be fixed; however, the sample 
obtained from each participating site will vary, depending on the available sample.
8.6. Data Management
 will perform the analyses described in this proposal using Statistical Analysis 
Software (SAS) application housed on 
 secure, large-capacity, high-performance 
Linux mainframe.  Experienced 
 programmers and analysts will perform all analyses.  
To ensure the integrity and quality of the study results, we will follow our programming 
validation life-cycle process for all analyses.  This includes quality-checking programs, logs, 
and output for accuracy according to relevant standard operating procedures.
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To ensure the integrity and quality of study results, 
 implements several practice 
standards for statistical programming, database management, and documentation for all 
projects involving databases analyses.  The following 3 steps will be undertaken to achieve 
this high level of quality:
•
Documentation of SAS programming;
•
Validation of SAS programs;
•
Database storage and retention.
8.6.1. Documentation of SAS Programming
To ensure smooth transitions of analytic methods and work among programmers, reviewers, 
and other project personnel, documentation of the following information will be created for 
each SAS program:
•
Project name;
•
Program name;
•
Program purpose;
•
Program author;
•
Date the program was completed;
•
Descriptions of subsequent changes and/or enhancements, with name of programmer 
and date for each.
This information will be incorporated into each program in the form of a header.  In addition to 
documenting this information in a general program header, each program will include detailed 
comments throughout to describe the purpose and method of specific programming statements.
8.6.2. Validation of SAS Programs
In this section, we describe a variety of programming validation methods, including log 
review, review of data listings, and independent programming, which will be used to ensure 
that our SAS programs function as intended.  The validation methods described in this 
section are not exhaustive, and additional measures will be implemented as appropriate.
8.6.3. Log Review
Programmers will review all SAS log files.  This procedure is a widely accepted, basic level 
of program validation.  The following issues must be addressed as part of a log review:
•
No errors should appear in a log file.
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•
If warning messages or messages related to uninitialized variables are permitted in the 
log file, the programmer will document why they are permitted.
•
The programmer will account for the number of observations reported at each 
executed data step, especially when the number of observations increases or 
decreases.
•
The log file will contain all lines of the program as it was saved at the time of 
execution, and it will contain only those lines of code.
8.6.4. Review of Data Listings and Tables of Summary Statistics
Because an error-free log file does not necessarily demonstrate that a SAS program has 
functioned as intended, programmers will produce cell frequencies, means, and other 
summary statistics on specific data items to demonstrate that the program results are valid.  
When appropriate, we also will have a separate analyst review these listings independent of 
the programmer.
8.6.5. Independent Programming
For highly complex programming tasks, a second programmer will attempt (if necessary) to 
independently reproduce output generated by the initial programmer.  If the outputs are 
equivalent, the test will be considered successful.  If the outputs are not equivalent, the 
programmers will evaluate the differences and make appropriate corrections.
8.6.6. Validation Documentation
•
For each SAS program used to produce final study outputs for presentation, 
 
will complete and store a formal SAS validation document.
8.6.7. Case Report Forms (CRFs)/Data Collection Tools (DCTs)/Electronic Data Record
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included patient.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.
To comply with privacy requirements, physicians (or the designated research team) will be 
abstracting the clinical and safety data directly from patients’ medical records to the eCRF, 
and neither Pfizer nor 
will have access to patients’ medical records.  To decrease 
chances of data-entry errors and resulting inaccuracies, data checks will be programmed into 
the eCRF, where possible, to improve the internal consistency of the data.  Physicians (or the 
designated research team) will be able to make changes to the data in the eCRF before it is 
submitted, and any requests for corrections to entries made in the eCRFs will be dated and 
explained (if necessary).  
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8.6.8. Database Storage and 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, eg, CRFs and hospital records), copies of all CRFs, safety 
reporting forms, source documents, and adequate documentation of relevant correspondence 
(eg, letters, meeting minutes, and telephone call reports).  The records should be retained by the 
investigator according to local regulations or as specified in the clinical study agreement, 
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 (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or to an independent third party arranged by Pfizer.
Study records must be kept for a minimum of 15 years after completion or discontinuation of 
the study, unless specific Pfizer protocols or 
policies explicitly prohibit this.  If any 
data-cleaning activities or other analyses need to be repeated for any reason, this retention 
procedure will allow quick and efficient access to the data sets.  If requested by Pfizer, the 
raw analytical files will be provided to Pfizer.
The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met.
8.7. Data Analysis
All measures described in Section 8.3 will be summarized descriptively through the tabular 
and graphical display of mean values, medians, ranges, and standard deviations of continuous 
variables of interest and frequency distributions for categorical variables.  Time-to-event 
outcomes (ie, overall survival, PFS, time to second-line initiation) will be described using the 
Kaplan-Meier method.  All analyses will be conducted using SAS (version 9.4 or later) 
statistical software.  Samples of patients who switched from the 4/2 to the 2/1 schedule from 
each country will be pooled and analyzed in aggregate.  The sample of patients from Brazil 
who initiated first-line sunitinib on the 2/1 schedule will be analyzed separately. Results may 
be described for up to 2 subgroups that will be determined after the initial review of the data
(eg, number of cycle on the 4/2 schedule).  
As this study is descriptive and designed to generate hypotheses, direct comparisons between 
outcomes on the 4/2 schedule and on the 2/1 schedule will not be conducted.  Potential 
confounders, such as characteristics that prompt the switch and other possible 
time-dependent factors (eg, dose modifications and delays), are not comprehensively 
collected or controlled for in this study design.  Variability in timing of the switch from a 
4/2 to a 2/1 schedule will affect the distribution of time-dependent outcomes after the switch 
(even in the absence of immortal-time bias), as some patients may switch “early” in their 
first-line therapy and others may switch “later.” Thus, causal inferences about the benefit of 
switching treatment schedules cannot be drawn.
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Detailed methodology for summary and statistical analyses of data collected in this study will 
be documented in a statistical analysis plan, which will be dated, filed and maintained by the 
sponsor.  The statistical analysis plan 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.  
8.8. Quality Control
The following data checks will be performed for all data collected in the eCRF:
•
Check for illogical or unusual data (eg, treatment starting prior to diagnosis);
•
Check for speeders (ie, abstractors who seem to skim through the eCRF by falling 
below a certain tolerance time interval of an estimated average duration needed for 
completing the form);
•
Check for responders with a typical unrealistic response pattern, such as always 
checking the same value in a numerical scale or responding in an erratic, implausible 
manner to certain questions;
•
Check for an extremely high percentage of “Do not know” or “Data not available” 
responses;
•
Check for an extremely high percentage of answering filter questions in a way so as 
to avoid having to answer subsequent questions in more detail.
The 
 Office of Quality Assurance (OQA) is an independent unit that reports to the 
Vice President of 
 and provides training on applicable regulations and guidelines, 
implements and maintains a series of standard operating procedures, and provides quality 
assurance monitoring for compliance with regulatory requirements.
 will work closely with the selected subcontractors to establish and ensure a complete 
integration of procedures for the project.  The OQA will perform audits and assessments that 
involve various aspects of the project for involved subcontractors, including but not limited 
to, education and training documentation.  Audits are conducted by the OQA according to 
established criteria in standard operating procedures and other applicable procedures.  The 
OQA reports quality assurance observations to the Project Director and facilitates corrective 
actions, if necessary.
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8.9. Limitations
Retrospective medical record reviews are subject to the following general limitations:

Patients selected for study inclusion represent a “convenience” sample, in that the 
records will be obtained from sites who are willing to participate in the study.  
Therefore, study findings may not be generalizable to the overall population of 
patients with metastatic RCC or sites where RCC is treated in the selected countries.

All data captured in the eCRF will be limited to information available in the patients’ 
medical records held by the sites participating in the study.  Information on health 
care services received outside the sites’ care setting that is not recorded in the medical 
record will be unavailable for this study (eg, treatment for AEs received through a 
separate hospital).

To increase the chance of random selection of eligible medical records at sites that 
estimate a larger than needed eligible population, abstractors will be asked to select 
medical records for patients whose last names begin with a randomly generated letter 
between A and Z.  Due to variations in the distribution of first letters among last 
names, patients may not have an equal probability of inclusion in the study.

Data will be entered directly by each site’s research team or PI and therefore may be 
subject to entry errors and resulting inaccuracies in reporting.  Although there will be 
data checks in place to improve internal consistency of the data, responses will not be 
validated against the patients’ medical records by an independent reviewer.

This study is designed to describe characteristics and outcomes of patients who 
switched from the 4/2 to the 2/1 sunitinib schedule.  Potential confounders, such as
characteristics that prompt the switch and other possible time-dependent factors (eg, 
dose modifications and delays), are not comprehensively collected or controlled in 
this study design.  Variability in timing of the switch from a 4/2 to a 2/1 schedule will 
affect the distribution of time-dependent outcomes after the switch (even in the 
absence of immortal-time bias), as some patients may switch “early” in their first-line 
therapy and others may switch “later.” Thus, causal inferences about the benefit of 
switching treatment schedules cannot be drawn.
8.10. Other Aspects
Not applicable.

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9. PROTECTION OF HUMAN SUBJECTS
9.1. Patient Information
The PIs at each site will be provided with a summary of the protocol, objectives, and 
methods as well as their rights and responsibilities prior to providing their consent to 
participate in the study.  Physician or participating site staff’s consent will be obtained 
electronically prior to participating in the medical record abstraction.
Patient medical record data may contain highly sensitive and private personal health 
information.  Therefore, the following data collection strategies will be implemented to 
ensure the data collected in this study strictly comply with definitions of deidentified or 
anonymous data:
•
At any point in this study, members of the PI’s direct health care team or designated 
research team are the only individuals with access to the patient’s medical record data 
containing potentially identifiable information.  The study team (ie,
 and 
Pfizer) will not view, obtain, or have access to any identifiable health information 
such as patient name, address, date of birth, or other personal identifiers.
•
Patient identifiers such as name, address, telephone number, e-mail address, health 
record/beneficiary number, biometric data, and photographs are not relevant to this 
study and will not be collected or viewed at any point by the study team.
As the data used in this study are anonymous, this study poses minimal risk to patients whose 
medical record data are analyzed.  With anonymous data, the risk of a breach of 
confidentiality is primarily from malicious system hacking in the presence of suboptimal 
network security in the case of electronic data collection.  Outside of network security risks, 
identification of a single patient by members of the research investigative team, based on a 
combination of limited demographic information and treatment information, would require 
(in addition to malicious intent) access to all medical records in a region (including those 
outside the physicians/sites participating in the study) and an extraordinary analytic effort, 
except, perhaps, in the case of exceedingly rare conditions, which the current study does not 
include.  Based on the study design and data collection procedures, the study team believes 
there is only a minimal/remote risk of identification of patients.
The PI’s in this study will be subject to different, albeit remote, risks compared with patients.  
It is conceivable that participation in the study may divert a small amount of the physicians’ 
time and resources away from clinical activities to allow for their participation in this 
research.  However, it is expected that these physicians will adequately manage their time.
Only the abstractors who directly enter the patient data into the secure eCRF will see explicit 
patient identifying information.  The web portal used for data collection is hosted in a secure 
data center.  This data center offers a secure environment that minimizes the chance of a 
security breach, thereby allowing access only to authorized persons with valid usernames and 
passwords.  Only anonymized data will be held at the data center.  As stated previously, to 
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protect the rights and freedoms of natural persons with regard to the processing of personal 
data, no protected health information will be collected, and thereby, no data containing 
patient identifiable information will be transferred to Pfizer.
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 when required by applicable laws.
9.2. 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.  If ethics 
requirements at a participating site or in a given country require informed consent, a waiver 
of informed consent will be sought.
9.3. Participation Withdrawal
Participating sites may withdraw from the study at any time at their own request, or they may 
be withdrawn at any time at the discretion of the investigator or sponsor for safety, 
behavioral, or administrative reasons.  If a site withdraws from the study and withdraws 
consent for disclosure of future information, no further evaluations should be performed, and 
no additional data should be collected.  The sponsor may retain and continue to use any data 
collected before such withdrawal of consent.
9.4. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
There must be prospective approval of the study protocol, protocol amendments, and other 
relevant documents (eg, 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.
9.5. 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 will follow generally accepted research practices 
described in the following:

Guidelines for Good Pharmacoepidemiology Practices (GPP) issued by the 
International Society for Pharmacoepidemiology (ISPE) 
https://www.pharmacoepi.org/resources/guidelines_08027.cfm.

Good Practices for Outcomes Research issued by the International Society for 
Pharmacoeconomics and Outcomes Research (ISPOR) 
http://www.ispor.org/workpaper/practices_index.asp.

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•
Good practices for real-world data studies of treatment and/or comparative 
effectiveness: Recommendations from the joint ISPOR-ISPE Special Task Force on 
real-world evidence in health care decision making
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5639372/.
Ethics review requirements and processes for retrospective studies vary between countries 
and are governed by local standards.  This study will be conducted in accordance with such 
standards in each country.
will work in collaboration with the site PIs to submit the necessary ethics review 
applications in each country at both the site and national levels, where applicable.  However, 
the site PIs will be responsible for submissions to the ethics review board (ERB), completion 
of notifications/submissions, and follow-up with ERBs to obtain final approvals where 
appropriate.  The following activities are anticipated:
•
Argentina:
•
No national-level approval by the Administración Nacional de Medicamentos, 
Alimentos y Tecnología Médica (ANMAT) required;
•
The site must be registered or accredited within the Jurisdiction of the Ministry of 
Justice;
•
ERB review is required at each of the participating sites.
•
Brazil:
•
No national-level approval by the Agência Nacional de Vigilância Sanitária 
(ANVISA) required;
•
Comissão Nacional de Ética em Pesquisa (CONEP) approval is required for at 
least one site, which will serve as the lead site; this serves as a national ethics 
approval;
•
ERB review is required at each of the participating sites.
•
Ecuador:
•
Approval is required by an Ethics Committee of Human Research (CEISH) 
recognized by the Ministry of Public Health;
•
ERB review is required at of the participating sites.
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
Colombia:

Notification to the Instituto Nacional de Vigilância de Medicamentos y Alimentos 
(INVIMA) is required;

ERB review is required at each of the participating sites.

Costa Rica:

National-level approval by the Consejo Nacional de Investigación en Salud 
(CONIS) required;

Approval is required by the Centro de Desarrollo Estratégico e Información en 
Salud y Seguridad Social (CENDEISSS);

ERB review is required at the participating sites.

Peru:

No national-level approval by the Instituto Nacional de Salud (INS) required;

Ethics Committee approval is required for each site (Ethics Committee must be 
registered with the INS competent authority).

Mexico:

Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)
approval is required;

Ethics Committee approval is required for each site (the Ethics Committee must 
be approved by the La Comisión Nacional de Bioética (COMBIOETICA) and 
COFEPRIS and approval must be current until the study ends.
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS
This study protocol requires human review of patient-level unstructured data; unstructured 
data refer to verbatim medical data, including text-based descriptions and visual depictions of 
medical information, such as medical records, images of physician notes, neurological scans, 
X-rays, or narrative fields in a database.  The reviewer is obligated to report adverse events 
(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 
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The requirements for reporting safety events on the non-interventional study (NIS) adverse 
event monitoring (AEM) Report Form to Pfizer Safety are as follows:

All serious and non-serious AEs with explicit attribution to any Pfizer drug that 
appear in the reviewed information must be recorded on the data collection tool and 
reported, within 24 hours of awareness, to Pfizer Safety using the NIS AEM Report 
Form.

Scenarios involving drug exposure, including exposure during pregnancy, exposure 
during breast feeding, medication error, overdose, misuse, extravasation, lack of 
efficacy, and occupational exposure associated with the use of a Pfizer product must 
be reported, within 24 hours of awareness, to Pfizer Safety using the NIS AEM 
Report Form.
For these AEs with an explicit attribution or scenarios involving exposure to a Pfizer product, 
the safety information identified in the unstructured data reviewed is captured in the Event 
Narrative section of the report form, and constitutes all clinical information known regarding 
these AEs.  No follow-up on related AEs will be conducted.
All the demographic fields on the NIS AEM Report Form may not necessarily be completed, 
as the form designates, since not all elements will be available due to privacy concerns with 
the use of secondary data sources.  While not all demographic fields will be completed, at the 
very least, at least one patient identifier (eg, gender, age as captured in the narrative field of 
the form) will be reported on the NIS AEM Report Form, thus allowing the report to be 
considered a valid one in accordance with pharmacovigilance legislation.  All identifiers will 
be limited to generalities, such as the statement “A 35-year-old female...” or “An elderly 
male...”  Other identifiers will have been removed.
Additionally, the onset/start dates and stop dates for “Illness”, “Study Drug”, and “Drug 
Name” may be documented  in month/year (mmm/yyyy) format rather than identifying the 
actual date of occurrence within the month/year of occurrence in the day/month/year 
(DD/MMM/YYYY) format.
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 
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Re-training must be completed on an annual basis using the most current Your Reporting 
Responsibilities training materials. 
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS
In the event of any prohibition or restriction imposed (eg, clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information which might influence the evaluation of the benefits and risks of a Pfizer 
product, Pfizer should be informed immediately.

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12. REFERENCES
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2.
Atkinson BJ, Kalra S, Wang X, Bathala T, Corn P, Tannir NM, et al. Clinical outcomes 
for patients with metastatic renal cell carcinoma treated with alternative sunitinib 
schedules. J Urol. 2014 Mar;191(3):611-8.
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Ezz El Din M. Sunitinib 4/2 versus 2/1 Schedule for patients with metastatic renal Cell 
carcinoma: tertiary care hospital experience. Clin Genitourin Cancer. 2017 
Jun;15(3):e455-e462.
4.
Kondo T, Takagi T, Kobayashi H, Iizuka J, Nozaki T, Hashimoto Y, et al. Superior 
tolerability of altered dosing schedule of sunitinib with 2-weeks-on and 1-week-off in 
patients with metastatic renal cell carcinoma--comparison to standard dosing schedule 
of 4-weeks-on and 2-weeks-off. Jpn J Clin Oncol. 2014 Mar;44(3):270-7.
5.
Najjar YG, Mittal K, Elson P, Wood L, Garcia JA, Dreicer R, et al. A 2 weeks on and 1 
week off schedule of sunitinib is associated with decreased toxicity in metastatic renal 
cell carcinoma. Eur J Cancer. 2014 Apr;50(6):1084-9.
6.
Boegemann M, Hubbe M, Thomaidou D, Blackburn S, Bent-Ennakhil N, Wood R, et al. 
Sunitinib Treatment Modification in First-Line Metastatic Renal Cell Carcinoma: 
Analysis of the STAR-TOR Registry. Anticancer Res. 2018 Nov;38(11):6413-22.
7.
Bracarda S, Iacovelli R, Boni L, Rizzo M, Derosa L, Rossi M, et al. Sunitinib 
administered on 2/1 schedule in patients with metastatic renal cell carcinoma: the 
RAINBOW analysis. Ann Oncol. 2015 Oct;26(10):2107-13.
8.
Jonasch E, Slack RS, Geynisman DM, Hasanov E, Milowsky MI, Rathmell WK, et al. 
Phase II study of two weeks on, one week off sunitinib scheduling in patients with 
metastatic renal Cell carcinoma. J Clin Oncol. 2018 Jun 1;36(16):1588-93.
9.
Lee JL, Kim MK, Park I, Ahn JH, Lee DH, Ryoo HM, et al. RandomizEd phase II trial 
of Sunitinib four weeks on and two weeks off versus Two weeks on and One week off 
in metastatic clear-cell type REnal cell carcinoma: RESTORE trial. Ann Oncol. 2015 
Nov;26(11):2300-5.
10.
International Agency for Research on Cancer. GLOBOCAN. Kidney—estimated 
incidence, all ages: both sexes. 2012 Available at: 
http://globocan.iarc.fr/old/summary_table_site-
html.asp?selection=10210&title=Kidney&sex=0&type=0&window=1&africa=1&ameri
ca=2&asia=3&europe=4&oceania=5&build=6&sort=0&submit=%C2%A0Execute%C2
%A0. Accessed on September 5, 2018.

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11.
Wong MCS, Goggins WB, Yip BH, Fung FDH, Leung C, Fang Y, et al. Incidence and 
mortality of kidney cancer: temporal patterns and global trends in 39 countries. Sci Rep. 
2017;7(1):15698.
12.
Sierra MS, Soerjomataram I, Antoni S, Laversanne M, Pineros M, de Vries E, et al. 
Cancer patterns and trends in Central and South America. Cancer Epidemiol. 
2016;44Suppl1:S23-42.
13.
Dekel Y, Koren R, Kugel V, Livne PM, Gal P. Significance of angiogenesis and 
microvascular invasion in renal cell carcinoma. Pathol Oncol Res. 2002;8(2):129-32.
14.
Oda T, Takahashi A, Miyao N, Yanase M, Masumori N, Itoh N, et al. Cell proliferation, 
apoptosis, angiogenesis and growth rate of incidentally found renal cell carcinoma. Int J 
Urol. 2003; 10(1):13-–18.
15.
Toge H, Inagaki T, Kojimoto Y, Shinka T, Hara I. Angiogenesis in renal cell 
carcinoma: the role of tumor-associated macrophages. Int J Urol. 2009 Oct;16(10):801-
7.
16.
Motzer RJ, Huston TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, et al. 
Overall survival and updated results for sunitinib compared with interferon alpha in 
patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27(22):3584-90.
17.
Houk BE, Bello CL, Poland B, Rosen LS, Demetri GD, Motzer RJ. Relationship 
between exposure to sunitinib and efficacy and tolerability endpoints in patients with 
cancer: results of a pharmacokinetic/pharmacodynamic meta-analysis. Cancer 
Chemother Pharmacol. 2010 Jul;66(2):357-71.
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Ravaud A . How to optimise treatment compliance in metastatic renal cell carcinoma 
with targeted agents. Ann Oncol. 2009; 20(Suppl. 19):i7–12.
13. LIST OF TABLES
None.
14. LIST OF FIGURES
Figure 1.
Site Selection, Feasibility Assessment, Contracting, and Data 
Collection Responsibilities.......................................................................15
Figure 2.
Study Design: First-Line Switch From 4/2 to 2/1 Sunitinib.....................16
Figure 3.
Study Design: Initiated First-Line 2/1 Sunitinib (Brazil Only)................17