Lung adenocarcinoma is a prevalent and aggressive subtype of non-small cell lung cancer (NSCLC). Mutations in the Kirsten rat sarcoma viral oncogene homologue (KRAS) represent key oncogenic drivers and are associated with poor prognosis. Sotorasib is a KRAS G12C inhibitor. It suppresses tumor growth by specifically and irreversibly locking the mutant KRAS protein. Currently, sotorasib is only approved for later-line treatment of KRAS G12C-mutated NSCLC. Here, we present a case of advanced NSCLC harboring a KRAS G12C and STK11 mutations. The patient received an exploratory first-line therapy with sotorasib combined with immunotherapy and chemotherapy, achieving significant and durable clinical benefit lasting 23 months, with manageable adverse events. This case highlights the potential of sotorasib in combination regimens as a first-line treatment strategy for KRAS G12C-mutated NSCLC and underscores the importance of individualized treatment planning. However, the use of sotorasib in the first-line setting remains an exploratory off-label approach and requires further clinical evidence to validate this treatment strategy.
Wang et al. (2026) studied this question.