Survival Endpoints for Treatment Evaluation in Subjects Treated for Metastatic Breast Cancer: Contribution of Real-life Databases
Conditions: Metastatic Breast Cancer
Sponsor: Institut Bergonié

    
 
 
  
 
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ASSOCIATION BETWEEN PROGRESSION FREE SURVIVAL AND 
OVERALL SURVIVAL IN WOMEN RECEIVING FIRST-LINE 
TREATMENT FOR METASTATIC BREAST CANCER:  
EVIDENCE FROM THE ESME REAL-WORLD DATABASE 
 
IB-2017DATECAN-ESME 
NCT03676257 
Version n°1.0 05/01/2020 
 
 
 
Coordinating Investigator 
Carine Bellera 
 
 
Scientific responsive 
Coralie Courtinard  
 
Clinical Research Unit 
Simone MATHOULIN-PÉLISSIER, MD, PhD  
Institut Bergonié, Bordeaux 
Head of the Unit 
  
 
  
 
 
  
  
 
 
 
 
 
SPONSOR 
INSTITUT BERGONIÉ 
 
 
 

Institut Bergonié 
Synopsis [Acronnyme] 
Synopsis_[Acronyme]_v0.X_DD/MM/YYYY 
 
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Title 
of 
the 
study  
ASSOCIATION BETWEEN PROGRESSION FREE SURVIVAL AND OVERALL SURVIVAL IN 
WOMEN RECEIVING FIRST-LINE TREATMENT FOR METASTATIC BREAST CANCER:  
EVIDENCE FROM THE ESME REAL-WORLD DATABASE 
Abbreviation  
of the trial 
DATECAN-ESME 
Sponsor 
Identification 
Institut Bergonié, Comprehensive Cancer, Bordeaux 
Coordinating 
Investigator 
Carine Bellera 
Scientific 
responsive  
Coralie COurtinard 
Number 
of 
investigational 
sites planned 
18 
Number 
of 
patients 
20033 
Duration of the 
study 
Retrospective study 
Medical 
conditions 
Metastatic breast cancer 
Rationale of the  
study 
Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer 
clinical trials.  
In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as 
an intermediate endpoint. 
Evidence remains scarce regarding the degree of association between PFS and OS. Our 
study aimed to describe the individual-level association between real-world PFS (rwPFS) 
and OS according to first-line treatment in female patients with mBC managed in real-
world setting for each BC subtype (defined by status for both hormone-receptor [HR] 
expression and HER2 protein expression/gene amplification). 
Objectives 
To estimate rwPFS, OS and association between rwPFS and OS according to first-line 
treatment in female patients with mBC managed in real-world setting for each BC subtype 
(defined by status for both hormone-receptor [HR] expression and HER2 protein 
expression/gene amplification). 
Study design  
Retrospective study 
The Epidemio-Strategy and Medical Economic (ESME) Research Program is a French 
academic initiative supporting the centralization of structured and non- structured 
data documented in the electronic health records (EHR) (clinical notes, pathology 
reports and radiology reports) of patients treated for malignant conditions in a unique 
secured web-based data platform available for researchers.  
The ESME mBC data platform is an EHR-derived database that gathers exhaustive data 
on consecutive patients who initiated a L1 treatment for mBC between 01 January 2008 
and 31 December 2017 in one of 18 French Comprehensive Cancer Centers 
(clinicaltrials.gov; NCT 03,275,311). Patients who only receive surgery of a breast-
related metastatic lesion ae not eligible for selection into the ESME mBC database 
Randomization 
and Treatment 
groups 
Not applicable 
Eligibility 
criteria 
All female patients older than 18 years diagnosed with mBC (de novo disease or first 
metastatic recurrence) between January 1, 2008, and December 31, 2017, and who 
received a L1 systemic treatment such as chemotherapy, endocrine therapy or targeted 

     
Institut Bergonié 
Synopsis [Acronyme] 
 
  
 
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therapy, whatever the sequence (monotherapy or combination of therapies using distinct 
mechanisms of actions, i.e., polytherapy).  
A treatment line is defined as all anti-cancer treatments received in the absence of tumor 
progression.  
Patients without informative data for tumor subtype are excluded (e.g., status for both 
HR expression and HER2 expression/gene amplification).  
Patients receiving radiation therapy or anti-resorptive drugs (e.g., bisphosphonates, 
denosumab) as unique treatment are not considered in the analysis.  
Patients are excluded if a second breast cancer was diagnosed before the onset of 
metastatic disease in order to limit potential inconsistencies between both breast cancer 
tumor subtypes and the metastases. 
Treatment 
schedule 
and 
route 
of 
administration 
This is a retrospective study, based on clinical records. 
Endpoints 
rwPFS : time from initial diagnosis of mBC to the date of disease progression (regional 
recurrence, progression, appearance/occurrence of metastases and distant recurrence) or 
death (any cause), whichever came first.  
OS : time from diagnosis of mBC to the date of death from any cause. 
Statistical 
analysis plan 
This is a retrospective study, based on clinical records. 
Sample size : On April 14, 2020, the ESME mBC database included a total of 23,697 mBC 
subjects. Of those, 20,033 satisfy the eligibility criteria for our study population 
 
Statistical Analysis Plan (SAP) 
Baseline characteristics will be summarized using frequency and percentage for qualitative 
variables. Median and inter-quartile range will be reported for quantitative variables. We 
will report frequencies and proportions for variables with missing or not documented 
information. No statistical test will be performed for the descriptive analyses. 
Median follow-up will be estimated using the reverse Kaplan–Meier Method. Survival data 
will be estimated using Kaplan–Meier method and we will report median survival times 
with their respective 95% confidence interval (95%CI). Data for patients without the 
events of interest will be censored at the date of last contact recorded in the database. 
We will estimate the individual-level association between rwPFS and OS using a Spearman 
rank correlation coefficient expressed as a value between 0 (no association) and 1 (perfect 
association) with 95% CI. Copula models allow one to jointly model two time-to-event 
variables. We will use a reviewed copula-based approach that introduced an iterative 
multiple imputation method for the estimation of the correlation coefficient. The strength 
of the rwPFS/OS association will be ranged according to the estimated correlation 
coefficient as follows: 0–0.19 is considered as very weak, 0.2–0.39 as weak, 0.40–0.59 as 
moderate, 0.6–0.79 as strong, and 0.8–1 as very strong correlation. We will estimate and 
report individual rwPFS/OS associations according to mBC subtype and first-line mBC 
treatment. 
Data will be analyzed using R software (v 3.6). 
IDMC 
Not applicable