Abstract

Objectives

This study aimed to demonstrate enhanced survival extrapolation methods using electronic health record-derived real-world data (RWD).

Methods

The study population included patients diagnosed of ER+/HER2− metastatic breast cancer who started first-line treatment with anastrozole or letrozole between November 18, 2014, and November 18, 2015. Two patient cohorts were constructed: a clinical trial cohort from digitized MONARCH-3 clinical trial results and a RWD cohort from a deidentified electronic health record-derived database. RWD patients were weighted to trial baseline covariate distributions. Standard parametric approaches were applied to trial data and a “best-fit” model was selected. We demonstrate traditional and enhanced hybrid (pooling with weighted RWD at start, 75%, or end of trial) extrapolation approaches.

Results

Observed and estimated 5-year progression-free survival (PFS) rates in extrapolating the trial control arm (n = 165) were comparable across all methods. Compared with the observed 5-year mean PFS in the RWD cohort (n = 118) of 20.4 months (95% confidence interval [CI] 16.9-23.8), there was some variation among studied methods. Best-fit standard parametric model (log-normal) had 5-year mean PFS of 21.3 months (95% CI 18.2-24.9), and for the hybrid methods in order of estimate conservativeness was start of trial (20.8 months; 95% CI 18.5-23.2), 75% of trial (21.3 months; 95% CI 18.1-24.5), and end of trial (21.8 months; 95% CI 18.8-25.2).

Conclusions

Our study leverages RWD to enhance long-term survival extrapolation. Future use cases should include applying patient eligibility criteria, weighting on baseline characteristics, and choice of time window to add RWD to trial data.