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.
Keywords: KRAS inhibitor; NSCLC; lung cancer; sotorasib; targeted therapy.
Sotorasib is an oral targeted therapy option for the treatment of non-small cell lung cancer (NSCLC) with KRAS G12C mutations. KRAS G12C is a mutation of the KRAS protein that leads to uncontrollable cell growth of the cancer cells. This mutation is present in 13% of patients with NSCLC. Even though this mutation occurs frequently, it has taken some time for a drug to be developed that can target this mutation due to the unusual shape of KRAS G12C and a lack of suitable sites on it for drugs to attach. The review describes how sotorasib works, summarizes the data from clinical trials supporting its use, and information for providers to consider when prescribing this medication.