Distribution of <i>KRAS</i> ^G12C Somatic Mutations across Race, Sex, and Cancer Type

Abstract

To the Editor: Hong et al. (Sept.24 issue) 1 present results of an early-phase clinical trial of sotorasib, which showed promising clinical benefit.Patients had non-small-cell lung cancer (NSCLC; 46%) or colorectal cancer (33%), and White patients constituted 76% of the cohort.As drugs are being developed for the previously "undruggable" KRAS G12C mutation, it is imperative to study the distribution of this mutation across sex, race, 2 and all cancers.We extracted data from the registry of the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE), version 8.0 3 (see the Methods section in Supplementary Appendix 1).We studied the distribution of KRAS G12C mutations in 32,138 patients with cancer across race (Asian, Black, and White) and sex and in 10 cancer types (Table S1.1 in Supplementary Appendix 2).A total of 2045 patients (6.4%) were Asian, 2355 (7.3%) were Black, and 27,738 (86.3%) were White.KRAS G12C mutations were compared according to race and sex, and P values were corrected by the Benjamini-Hochberg method to determine false discovery rate-corrected Q values, which were considered significant when Q was less than 0.05.KRAS G12C mutations were identified in 1867 samples, most frequently in patients with NSCLC (1443 of 10,444 [13.8%]).KRAS G12C mutations were identified in 3.5% of patients (74 of 2105) with cancer of unknown primary site, 3.3% of patients (12 of 368) with appendiceal cancer, 3.2% of patients (234 of 7402) with colorectal cancer, and 3.1% of patients (7 of 223) with small-bowel cancer (Fig. 1A, and Table S1.2 in Supplementary Appendix 2).Among patients

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