Characterization of a Real-World Response Variable and Comparison with RECIST-Based Response Rates from Clinical Trials in Advanced NSCLC
Xinran Ma, Lawrence Bellomo, Kelly Magee, Caroline S. Bennette, Olga Tymejczyk, Meghna Samant, Melisa Tucker, Nathan C. Nussbaum, Bryan Bowser, Joshua Kraut, Ariel B. Bourla
Abstract
INTRODUCTION: Effectiveness metrics for real-word research, analogous to clinical trial ones, are needed. This study aimed to develop a real-world response (rwR) variable applicable to solid tumors and to evaluate its clinical relevance and meaningfulness. METHODS: This retrospective study used patient cohorts with advanced non-small cell lung cancer from a nationwide, de-identified electronic health record (EHR)-derived database. Disease burden information abstracted manually was classified into response categories anchored to discrete therapy lines (per patient-line). In part 1, we quantified the feasibility and reliability of data capture, and estimated the association between rwR status and real-world progression-free survival (rwPFS) and real-world overall survival (rwOS). In part 2, we investigated the correlation between published clinical trial overall response rates (ORRs) and real-world response rates (rwRRs) from corresponding real-world patient cohorts. RESULTS: In part 1, 85.4% of patients (N = 3248) had at least one radiographic assessment documented. Median abstraction time per patient-line was 15.0 min (IQR 7.8-28.1). Inter-abstractor agreement on presence/absence of at least one assessment was 0.94 (95% CI 0.92-0.96; n = 503 patient-lines abstracted in duplicate); inter-abstractor agreement on best confirmed response category was 0.82 (95% CI 0.78-0.86; n = 384 with at least one captured assessment). Confirmed responders at a 3-month landmark showed significantly lower risk of death and progression in rwOS and rwPFS analyses across all line settings. In part 2, rwRRs (from 12 rw cohorts) showed a high correlation with trial ORRs (Spearman's ρ = 0.99). CONCLUSIONS: We developed a rwR variable generated from clinician assessments documented in EHRs following radiographic evaluations. This variable provides clinically meaningful information and may provide a real-world measure of treatment effectiveness.