A pancancer analysis of KRAS alterations in Chinese population.

e15127 Background: Kirsten rat sarcoma viral oncogene homologue (KRAS) is the most frequently mutated oncogene in human cancers. Sotorasib (AMG 510) has shown promising anticancer activity in patients with heavily pre-treated KRAS p.G12C mutant solid tumors. Here, we provide an overview of genomic diversity of KRAS alterations in a large cohort of Chinese patients. Methods: Molecular profiles of 16,654 tumor specimens were obtained using gene-panel target-capture next-generation sequencing, and classified based on the presence and subtypes of KRAS mutation. Tumor mutation burdens (TMB) were calculated using an Acornmed panel with 808 cancer-related genes. Results: In total,15.04% (2505/16654) of pan-cancer patients harbored RAS mutations, and 13.58% (2262/16654) patients carried KRAS mutations in the current study. Five main subtypes of KRAS mutation were detected including G12D (642, 28.38%), G12V (392, 17.33%), G12C (354, 15.65%), G13 (220, 9.73%), G12A (101, 4.47%). In our cohort, the highest KRAS G12C mutation frequency tumor type was lung cancer (12.33%) followed by colorectal cancer (1.99%), which is comparable with the previously published data. Among all patients with KRAS G12C mutation, 77.40% (274/354) of the patients were male and 22.60% (80/354) were female. Tumor mutation burdens (TMB) were calculated for 151 samples of all the 352 KRAS G12C mutation samples. The median TMB was 10.15 mut/Mb with 50.99%≥10 mut/Mb and 14.57%≥20 mut/Mb. However, according to the results of CodeBreaK 100 exploratory analysis at the 2021 ASCO annual meeting, among all patients with KRAS G12C mutation, 17.86% of the patients had ≥ 10 mut /Mb, which was defined as TMB-high. Therefore, it can be found that the TMB of domestic and foreign patients is different. Conclusions: Genomic alterations in KRAS are widespread among Chinese pan-cancer patients. Results of CodeBreaK 100 exploratory analysis presented at the 2021 ASCO Annual Meeting showed no significant difference (40% vs 42%) in objective response rates between TMB high (≥ 10 mut/Mb) and TMB low (< 10 mut/Mb). Based on our data, the threshold of TMB high in the Chinese population should be higher. The molecular marker exploration of AMG 510 efficacy in the Chinese population needs to be further carried out and confirmed.