Sotorasib for the treatment of locally advanced/metastatic non-small cell lung cancer.

Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation is prognostic of poor survival for patients with non-small cell lung cancer (NSCLC). KRAS G12C mutations occur in 13% of NSCLC cases and despite the frequency of this mutation, advances in drug development against KRAS have historically been impeded due to the extremely high affinity of KRAS for guanosine triphosphate (GTP) and the lack of a binding pocket on the surface of KRAS that is suitable for drug binding. Sotorasib, a first-in-class, highly selective KRAS G12C inhibitor overcomes this issue by irreversibly binding in the switch-II pocket. Sotorasib was granted accelerated FDA approval for the treatment of KRASG12C-mutated locally advanced/metastatic NSCLC who have received at least one prior systemic therapy. This review summarizes the pharmacology, clinical efficacy, adverse effects, and clinical considerations of sotorasib.