Value of Comprehensive Genomic Profiling on Clinical Actionability and Treatment in Advanced Cancer Patients
oregon; portland; chiles
Introduction: Precision therapies and immunotherapies have revolutionized cancer care, with novel genomic biomarker-associated therapies being introduced into clinical practice rapidly. We assessed the utility of comprehensive genomic profiling (CGP)-based testing for identifying biomarkers associated with approved therapies, and therapies in precision medicine basket clinical trials (CT) and the therapies received in the line subsequent to CGP testing across a large cohort of advanced cancer patients in the Providence Health System. Methods: Advanced cancer patients were tested utilizing the Providence CGP workflow between 2019-2021. 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: A total of 2,028 advanced cancer patients were tested with CGP and followed up for cancer care management at Providence; 52% were female, 83% were white, and median age was 66 years. Across 31 tumor types, the most commonly tested were lung (27%), bowel/colon (16%), and breast (10%). Forty-seven percent (964) of patients had at least one actionable biomarker for an approved and/or guideline recommended targeted therapy (based on OncoKB levels 1,2, R1), and 53% were eligible for at least one of three basket trials at the time of testing. Of the CGP tested patients, 14% 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 (663 [33%]), chemotherapy + immunotherapy (IO) (347 [17%]), IO only (269 [13%]), targeted therapy in community setting (361 [18%]), targeted therapy in CT setting (79 [4%]), and off-label use of targeted therapy (7 [0.3%]). Of 361 patients who received a targeted therapy, 227 (63%) had an associated oncogene whereas 134 (37%) were treated based on approved disease-specific indications. Conclusions: The rate of clinical actionability for approved and guideline recommended therapies and for basket CTs is considerable after testing with CGP, resulting in precision therapies (targeted therapy and immunotherapy) rapidly eclipsing chemotherapy as major treatment modalities. We expect the value of CGP to increase as biomarker actionability transforms clinical practice.
Bifulco, C; Bapat, B; Weerasinghe, R; Meng, R; Dowdell, A; Vita, A; Chang, S; Campbell, M; Schroeder, B; and Piening, B, "Value of Comprehensive Genomic Profiling on Clinical Actionability and Treatment in Advanced Cancer Patients" (2022). Articles, Abstracts, and Reports. 6999.