Background: There is growing interest to assess treatment effect with clinical endpoints that are reflective of real world clinical practice based on data systemically collected from the electronic health record (EHR). This study compared real world PFS (rwPFS) among a cohort of female patients (pts) treated with letrozole (LET) monotherapy as first-line therapy for metastatic breast cancer (MBC) in routine clinical practice to PFS using RECIST criteria from the LET alone cohort in a randomized clinical trial (PALOMA-2).

Methods: For rwPFS, assessments were based on clinician notes, radiological reports, and pathological reports available in the EHR. Data were extracted from the EHR using technology-enabled abstraction; relevant documents were presented to trained human experts and data were entered into an electronic interface mimicking a case report form, with centralized management and quality controls. The patient cohort was derived from a large, longitudinal, demographically and geographically diverse EHR database of pts receiving cancer care at U.S. community-based and academic clinics (Flatiron Health); pts were all females who began treatment with LET for MBC as first-line treatment between January 1, 2011 and September 30, 2015. PFS in the clinical trial used a conventional definition based on RECIST; data were from the Pfizer clinical study PALOMA-2 database; 222 post-menopausal women in the LET alone arm met pre-specified inclusion/exclusion criteria and assessment intervals with enhanced data collection as previously detailed (Finn, NEJM 2016). All data were de-identified. Propensity score matching using a nearest neighbor algorithm with caliper=0.10 (maximum difference in propensity scores for a match) was performed to assess the consistency between the two approaches to PFS assessment. Kaplan-Meier estimates of median rwPFS/PFS are reported.

Results: 107 pts met eligibility criteria from the EHR subset. Pts were younger and had less extensive disease in the PALOMA 2 cohort: The mean age was 60.6 vs 68.6 years and the proportion stage IV at diagnosis was 32.4% versus 39.3% in the LET alone cohort in PALOMA-2 compared to the EHR cohort, respectively. Propensity matching with caliper=0.10 based on age, stage at diagnosis and # of disease sites identified 79 pts from each cohort.

Summary of Progression-Free Survival in Matched Data Using Propensity Score Matching Method (Kaplan-Meier estimates)

  rwPFS RECIST PFS 
Source Flatiron PALOMA-2 
Unmatched results     
N (pts) 107 222 
median PFS (months) 18.7 14.5 
95% Confidence Interval (14.6, 24.1) (12.9, 17.1) 
Matching with Caliper (=0.10)     
N (pts) 79 79 
median PFS (months) 18.5 19.2 
95% Confidence Interval (13.7, 24.1) (13.7, not estimated) 
  rwPFS RECIST PFS 
Source Flatiron PALOMA-2 
Unmatched results     
N (pts) 107 222 
median PFS (months) 18.7 14.5 
95% Confidence Interval (14.6, 24.1) (12.9, 17.1) 
Matching with Caliper (=0.10)     
N (pts) 79 79 
median PFS (months) 18.5 19.2 
95% Confidence Interval (13.7, 24.1) (13.7, not estimated) 

Conclusion: This analysis showed concordance between rwPFS and RECIST-based PFS for LET-treated MBC matched pts using a caliper=0.10 in the first line setting. Clinically meaningful information on treatment effect could be derived from a rwPFS assessment based on EHR data abstraction that incorporates proper quality controls.

Impact: These data increase confidence in the use of rwPFS as a primary outcome in real-world studies.

Citation Format: Bartlett CH, Mardekian J, Cotter M, Huang X, Zhang Z, Parrinello CM, Abernethy AP, Koehler M. Concordance of real world progression free survival (PFS) on endocrine therapy as first line treatment for metastatic breast cancer using electronic health record with proper quality control versus conventional PFS from a phase 3 trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-17-03.