The distribution of genetic mutations correlated with resistance to KRASG12C inhibitors in Chinese patients with lung cancer.

• DOI: 10.1200/jco.2022.40.16_suppl.3141
• Publication Date: 2022-06-06T16:09:21Z
• Authors: Shengcheng Lin; Kai Ma; Yafei Xu; Xinyi Liu; Xiaochun Huang; Mengli Huang
• Keywords: 03 medical and health sciences; 0302 clinical medicine; 3. Good health

3141 Background: In lung cancer, p.G12C is the most frequent variant in Kirsten rat sarcoma viral oncogene homologue (KRAS) gene. KRAS G12C inhibitors have shown promising efficacy cancer recent clinical trials, acquired resistance, however, eventually occurred patients. Preliminary studies revealed that a number of genetic mutations were correlated with resistance to this type drugs, including secondary mutations, activating RTK-RAS-MAPK signaling pathways members, rearrangements and copy gain. To clarify potential application inhibitors, herein we analyzed distribution reported gene alterations large natural group Chinese as well mutation landscape subset patients suspected resistant mutations. Methods: A total 32878 early-stage, late-stage without treatment or previously treated study. Wide NGS panel testing was used detected single nucleotide variants (SNV), (CNV) oncogenic rearrangements. Results: 2767 (8.4%) cases, which common (30.86%). Among 854 (2.6%) harbored G12C, 75 (10%) carried above such G12D/R/V (n = 7). Fusions (20%) observed only coloretal unexpectedly corhort, EML4-ALK 1), FGFR1-MECOM EWSR1-CHEK2 2), SPEN-KAZN MET-KCNB2 NOTCH2-NOTCH2NLA 5), SMARCA4-DNAH8 LIPM-FAS 1). Furthermore, (46.7%), MYC (25.3%) MET (10.7%) amplified. TP53 (66%), LRP1B (25%), STK11 (22%) frequently mutated genes. It noteworthy STK11/KEAP1 /NFE2L2 nearly 30% Conclusions: The results our analysis suggested about 10% G12C-mutated would be inhibitors. Moreover, small co-mutated genes negatively related immunotherapy NSCLC, indicating they also inappropriate for immunotherapy.