Abstract 1786P
Background
Recently, KRAS G12C inhibitor showed clinical activity in NSCLC patients harboring a KRAS G12C mutation. Importantly, the prevalence of KRAS G12C mutations displayed significant differences according to sex, ethnic group, and cancer type. To optimize clinical trial design, it is important to analyze the distribution of KRAS G12C mutations in larger numbers of non-White populations.
Methods
Using next-generation sequencing (OncoPanscan, Genetronhealth), we examined the prevalence of KRAS G12C somatic mutations in 41,913 cancer patients from multiple centers in 15 cancer types, we also obtained data from the registry of the AACR Project GENIE.
Results
KRAS G12C mutations were identified in 911 Chinese cancer patients, most frequently in lung cancer (732 of 22761 [3.22%]) and colorectal cancer (118 of 5064 [2.33%]). KRAS G12C mutations were also identified in 1.87% of patients with pancreatic cancer (16 of 855), 1.49% of biliary tract cancer patients (14 of 941), 0.50% of gastric cancer, 0.36% with hepatocellular carcinoma, five with brain tumors, three females with uterine cancer, two males with sarcoma, one each female with esophageal carcinoma, peritoneal carcinoma, cervical carcinoma, squamous cell carcinoma of the sphenoidal sinus, as well as one each male patient with melanoma and renal pelvis carcinoma. We compared our results with 32,138 patients from the AACR GENIE registry which showed that KRAS G12C mutations occurred more often in White female patients than in White male patients with NSCLC or colorectal cancer. Interestingly, among Chinese lung cancer patients, KRAS G12C mutations occurred more often in males than in females (4.85% vs 1.19%; OR, 4.2; 95% CI, 3.5 to 5.1; P <0.001). Among Chinese patients with colorectal cancer, male patients were not enriched for KRAS G12C mutations more than female patients (2.42% vs 2.19%; OR, 1.1; 95% CI, 0.8 to 1.6; P>0.05).
Conclusions
We found that KRAS G12C somatic mutations are common in Chinese patients with lung cancer and colorectal cancer. Our data confirmed the presence of differences according to sex and ethnic group in the distribution of KRAS G12C mutations in various cancer types. Clinicians should incorporate these differences when designing KRAS G12C inhibitor clinical trials in the Asian population.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
X. Li, T. Ma: Financial Interests, Personal, Full or part-time Employment: Genetron Health (Beijing) Technology, Co. Ltd.. All other authors have declared no conflicts of interest.