Combination therapy of sotorasib and docetaxel overcomes resistance to sotorasib alone in KRAS G12C mutant lung adenocarcinoma.

Mutations in the KRAS gene are the most common gain-of-function mutations found in lung adenocarcinomas. The most prevalent mutation, KRAS G12C, occurs in 13% of lung adenocarcinomas. Sotorasib is an irreversible small molecule inhibitor that targets KRAS G12C. Previous studies have shown that treatment with sotorasib leads to the regression of KRAS G12C-mutated tumours. However, KRAS G12C often occurs alongside other mutations, such as TP53, STK11 and KEAP1, which are associated with poor prognosis in advanced NSCLC when treated with sotorasib monotherapy. We present a case of metastatic NSCLC with KRAS G12C, TP53 and STK11 mutations that did not respond to sotorasib monotherapy. The patient received combination therapy with sotorasib and docetaxel, which resulted in remarkable efficacy. This case supports further investigation of sotorasib in combination with chemotherapy for treating KRAS G12C-mutated NSCLC with co-mutations.