Identification of clinically actionable biomarkers via routine comprehensive genomic profiling across a large community health system.
oregon; portland; chiles
Background: 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) 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 CGP and compared with results from an in silico 50-gene panel based on a previously utilized lab-developed test at Providence. Clinical actionability was assessed based on OncoKB and alterations were assigned as: FDA recognized (Level 1), standard of care (Level 2), FDA approved/investigational drug in another indication or having compelling clinical evidence (Level 3). CT matching was assessed based on enrollment criteria for ASCO-TAPUR, NCI-MATCH and My Pathway CTs at time of testing. Pooled electronic medical record and genomic data were curated and standardized. Results: Of the 3,218 advanced cancer patients tested with CGP, 52% were female, 80% were white, and median age was 67 years. Across 31 tumor types, the most commonly tested were lung (26%), bowel/colon (16%), and breast (9%). Overall, 48% of patients tested with CGP harbored at least one actionable biomarker (OncoKB Levels1/2/3). Clinical actionability was significantly higher in the CGP cohort compared to the in silico cohort based on presence of at least one Level 1 biomarker (45% vs. 19%, p < 0.001). CGP cohort had higher proportion of patients with multiple/co-occurring Level 1 biomarkers compared to in silico cohort (20% vs. 9%, p < 0.001). Of the most prevalent tumor types, 57% lung, 94% bowel/colon, and 37% breast had Level 1 alterations with CGP testing. Notably, 49% of CGP cohort vs. 23% in silico cohort (p < 0.001) harbored a biomarker matching to one or more arms of the three basket CTs. Conclusions: CGP and small panel testing can both identify patients eligible for approved therapies and/or basket CTs with CGP having significantly higher clinical actionability and CT eligibility. We expect value of CGP to increase as biomarker actionability transforms clinical practice.
Weersinghe, Rosohanthi K.; Meng, Ryan; Dowdell, Alexa K.; Bapat, Bela; Vita, Ann; Schroeder, Brock; Stein, Alisha; Harold, Lauren; Schmidt, Mark; Chang, Shu-Ching; Ward, Thomas; Wagner, Josiah; Piotrowski, Stanley; Febbo, Phillip G.; Bifulco, Carlo; and Piening, Brian, "Identification of clinically actionable biomarkers via routine comprehensive genomic profiling across a large community health system." (2022). Articles, Abstracts, and Reports. 7000.