The GENIE BPC NSCLC cohort: a real-world repository integrating standardized clinical and genomic data for 1,846 patients with non-small cell lung cancer.

PURPOSE: We describe the clinical and genomic landscape of the non-small cell lung cancer (NSCLC) cohort of the AACR Project GENIE Biopharma Collaborative (BPC).

EXPERIMENTAL DESIGN: 1,846 patients with NSCLC whose tumors were sequenced from 2014 to 2018 at four institutions participating in AACR GENIE were randomly chosen for curation using the PRISSMMÔ data model. Progression-free survival (PFS) and overall survival (OS) were estimated for patients treated with standard therapies.

RESULTS: In this cohort, 44% of tumors harbored a targetable oncogenic alteration, with EGFR (20%), KRAS G12C (13%) and oncogenic fusions (ALK, RET and ROS1; 5%) as the most frequent. Median OS (mOS) on first-line platinum-based therapy without immunotherapy was 17.4 mo (95% confidence interval (CI) 14.9,19.5 mo). For second-line therapies, mOS was 9.2 mo (95% CI 7.5,11.3 mo) for immune checkpoint inhibitors (ICI) and 6.4 mo (95% CI 5.1,8.1 mo) for docetaxel +/- ramucirumab. In a subset of patients treated with ICI in the second-line or later setting, median RECIST PFS (2.5 mo; 95% CI 2.2, 2.8) and median real-world PFS based on imaging reports (2.2 mo; 95% CI 1.7,2.6) were similar. In exploratory analysis of the impact of tumor mutational burden (TMB) on survival on ICI treatment in the second-line or higher setting, TMB z-score harmonized across gene panels was associated with improved OS (univariable HR 0.85, p=0.03, n=247 patients).

CONCLUSIONS: The GENIE BPC cohort provides comprehensive clinico-genomic data for patients with NSCLC, which can improve understanding of real-world patient outcomes.