Clinical actionability and therapy selection for advanced NSCLC patients tested using comprehensive genomic profiling
oregon; chiles; genomics
Background: Comprehensive genomic profiling (CGP) enables physicians to recommend advanced cancer treatments at the individual level by identifying patients that are likely and unlikely to benefit from targeted therapy or immunotherapy (IO). We assessed the utility of CGP-based testing for identifying biomarkers associated with approved therapies, and therapies in precision medicine basket clinical trials (CT) across a large cohort of advanced NSCLC patients in the Providence health system. Methods: Advanced cancer patients were tested utilizing the Providence CGP workflow between 2019 and 2021. Clinical actionability was assessed for patients based on OncoKB Tier 1 AMP/ASCO/CAP categorization: FDA recognized (Level 1), standard of care (Level 2), and standard of care predictive of resistance to an FDA approved drug (Level R1). CT matching was assessed based on enrollment criteria for ASCO-TAPUR, NCI-MATCH and My Pathway CTs at time of testing. Systemic therapy post CGP-testing was assessed among patients whose care was managed at Providence post CGP testing. Pooled electronic medical record and genomic data were curated and standardized. Results: 466 advanced NSCLC cancer patients were tested with CGP and followed up for cancer care management at Providence, 49% were female, 83% were white, and median age was 69 years. 59% (277) had at least 1 actionable biomarker for an approved and/or guideline recommended targeted therapy (based on OncoKB levels 1,2, R1), and 61% were eligible for at least 1 of 3 basket trials. Of the CGP tested patients, 9% did not receive any cancer directed therapy and/or received only supportive care. Patients were treated using the following systemic therapies in line following CGP testing: chemotherapy only (97[21%]), chemotherapy + IO (140 [30%]), IO only (83 [18%]), targeted therapy in community setting (91 [20%]), targeted therapy in CT setting (7 [2%]), and off label use of targeted therapy (2 [0.4%]). Of 91 patients who received targeted therapy, 84 (92%) had an associated oncogene while 7 (8%) were treated based on approved NSCLC-specific indications. Conclusions: CGP results in high proportion of patients eligible for both on-label therapies and for genomically-informed clinical trials. Moreover, comprehensive detection of both targeted and IO biomarkers simultaneously leads to optimal treatment selection. Conflict of interest: Ownership: Bela Bapat and Brock Schroeder are employees of Illumina, Inc. Corporate-sponsored Research: Brian Piening is recipient of a research grant from Illumina Inc.
Earle A. Chiles Research Institute
Bapat, B; Weerasignhe, R; Meng, R; Dowdell, A; Chang, SC; Schroeder, B; Bifulco, C; and Piening, B, "Clinical actionability and therapy selection for advanced NSCLC patients tested using comprehensive genomic profiling" (2022). Articles, Abstracts, and Reports. 6854.