Characterization of a Real-World Response Variable and Comparison with RECIST-Based Response Rates from Clinical Trials in Advanced NSCLC

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. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01659-0.

Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non–Small Cell Lung Cancer Trials Using Real-World Data

“…In metastatic breast cancer, estimates of rwRR were similar to the ORR in the PALOMA-2 trial (22). Notably, in a recent study by Ma and colleagues (17) in which 12 different cohorts were evaluated, rwRR estimates closely mimicked trial ORR estimates. In this study, although the point estimates for rwRR were higher than ORR in IMpower150-WT, none of the comparisons between any rwRR and its corresponding trial ORR was statistically significant.…”

Pan-cancer landscape ofCD274(PD-L1) rearrangements in 283,050 patient samples, its correlation with PD-L1 protein expression, and immunotherapy response

“…Treatment was considered discontinued due to change in line of therapy or death of the patient, all others were censored. Real-world response data (available for N=1 patient) was defined as the clinician assessment of change in disease burden following radiographic imaging during a line of therapy 32…”

Concordance of Clinician-Documented and Imaging Response in Patients With Stage IV Non–Small Cell Lung Cancer Treated With First-Line Therapy

“…4,[6][7][8] Our work focused on deidentified EHR-derived data; previously, our team characterized a response variable based on clinician-assessed response (CAR, referred to in prior publications as "real-world response"). 9 This variable, derived from EHR notes anchored at imaging assessment time points throughout lines of systemic therapy, relies on the treating clinician's written synopses of patients' status, not solely on radiology reports. We compared cohort-level response-rate estimates using clinical trial RECIST and CAR on analogous patient cohorts side by side, 9 and investigated the correlation between end point results with either variable, accounting for differences in cohort-level patient characteristics.…”

“…9 This variable, derived from EHR notes anchored at imaging assessment time points throughout lines of systemic therapy, relies on the treating clinician's written synopses of patients' status, not solely on radiology reports. We compared cohort-level response-rate estimates using clinical trial RECIST and CAR on analogous patient cohorts side by side, 9 and investigated the correlation between end point results with either variable, accounting for differences in cohort-level patient characteristics. 9 The CAR variable could provide clinically meaningful information comparable to RECIST at the cohort level, but the relationship between CAR and standardized, centralized, and radiologist-measured response (RECIST 1.1) at the patient-level within the same cohort remained an open question.…”