Lack of evidence to support large-panel genomic testing in treatment selection for malignant melanoma.

Abstract

e22027 Background: Genomic profiling informs clinical decision-making for malignant melanoma (MM) as specific tumor mutations can be treated with targeted therapy (TT). However, given the range of different panel sizes available and increasing use of immune checkpoint inhibitors (ICI), the clinical significance of upfront, large-panel genomic profiling in MM remains undetermined. Herein, we investigate the impact of panel size and targetable mutational status on first-line treatment selection and outcomes of MM patients from 9 different institutions. Methods: We analyzed data for 1,341 MM patients from 3 cohorts. Cohort 1 included 169 patients enrolled at NYULH and profiled with the 50 gene Ion Torrent panel (IT). Cohort 2 included 256 patients enrolled at MSKCC, profiled with the 400-gene MSK-IMPACT panel (MSK-I). Cohort 3 included 916 patients enrolled at 7 different sites, profiled with whole exome sequencing (WES). Data for cohorts 2 and 3 were extrapolated from publicly available data using cBioPortal. We tested associations between molecular data, treatment choice and overall survival (OS), adjusting for baseline characteristics when available. Results: Treatment information was available for 100%, 25%, and 0% of patients in cohort 1, 2 and 3, respectively. Stage was available for all of cohort 1 (III, n = 68; IV, n = 101) and cohort 2 (III, n = 2; IV, n = 254), but in only 23% of cohort 3 (III, n = 184; IV n = 25). For the IT and MSK-I, BRAF and NRAS were among the top 5 most commonly mutated genes, whereas for WES only BRAF was in the top 5. In cohort 1, 36% (16/45) of BRAF MUT patients received first-line TT vs 25% (66/256) in cohort 2. There was no significant difference for BRAF MUT patients treated with ICI vs. TT in cohort 1 in OS (P = 0.19), nor for BRAF MUT patients from cohort 1 treated with ICI vs. those from cohort 2 treated with TT (OS P = 0.762). Conclusions: Publicly available datasets provide population-level data, however the heterogeneity and deficiency of reported clinical information limits their value and calls for data standardization. Without evidence of clear clinical benefit of a larger panel size, there is a rationale for adopting smaller, more cost effective panels in MM.