Abstract 657P
Background
KRAS is a frequently mutated proto-oncogene in cancer, with the KRAS G12C mutation being a potential target for novel small-molecule inhibitors. To elucidate the landscape of KRAS mutations in AME, we analyzed a database of ctDNA results from advanced NSCLC patients tested as part of standard clinical practice.
Methods
We retrospectively analyzed KRAS mutations in advanced NSCLC patient from AME who underwent Guardant360® gene panel testing between Nov 2016 and Jun 2024.
Results
Among 6127 NSCLC patients with ctDNA detected, KRAS alterations were found in 14.1% (n=868). There was a higher prevalence in men (16%; 516/3141) than in women (12%; 352/2986). Prevalence of KRAS in East Asian countries (South Korea 13%, Japan 12%, Taiwan 12%, Hong Kong 12%) was lower compared to Middle East and Central Asian countries (Israel 20%, United Arab Emirates 19%, Vietnam 19%, Singapore 14%). Among 868 patients whose tumors had KRAS alterations, 25% (n=222) were age 60 years or younger. The most common mutations occurred in exon 2 at G12: G12C 24% (n=205), with a higher prevalence in men (30%) than in women (15%); G12D 21%; G12V 15%; G12R 2%; and G12F 1%. Outside exon 2, Q61 was most commonly mutated residue: Q61H 5%, Q61L 1%, and Q61R 1%. Co-alterations of EGFR were observed in 18% (157/868) of cases, including EGFR L858R (32%, n=50), exon 19 deletion (31%, n=49), and T790M (15%, n=23). There was significant enrichment for alterations in STK11, ARID1A, and SMAD4 in the KRAS-mutated group, while EGFR, EML4, ERBB2, and FANCA alterations were enriched in the KRAS wild-type group.
Conclusions
This large ctDNA-based study in AME identified KRAS mutation in 14.1% of advanced LC patients, lower than reports of LC patients from Europe or North America. Similar to the West, KRAS G12 mutations are the most common, with KRAS G12C nearly twice as common in men than in women. Furthermore, co-existence of EGFR and KRAS mutations occurs approximately 18% KRAS cases representing a diagnostic and therapeutic challenge worthy of further study.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
R. Bharat, S. Olsen, N. Joshi: Financial Interests, Institutional, Full or part-time Employment: Guardant Health. S.S. Jain: Financial Interests, Personal, Stocks or ownership: Guardant Health; Financial Interests, Institutional, Full or part-time Employment: Guardant Health. All other authors have declared no conflicts of interest.