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KRAS G12C Targeted Therapy — RACP Adult Medicine MCQ

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HardMedical OncologyKRAS G12C Targeted TherapyRACP Adult Medicine

A 60-year-old man with recently diagnosed lung adenocarcinoma (stage IV, EGFR wild-type, ALK negative, PD-L1 1%) undergoes molecular profiling. Testing reveals a KRAS G12C mutation. What targeted therapy is available?

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Correct answer: C — Sotorasib

KRAS G12C mutations occur in ~13% of NSCLC adenocarcinomas. Sotorasib (Lumakras) was the first KRAS G12C inhibitor approved based on the CodeBreaK 100 trial, showing a 37% response rate in previously treated NSCLC. Adagrasib is another option. These agents irreversibly bind the inactive GDP-bound form of KRAS G12C. KRAS was historically considered 'undruggable' – these represent a breakthrough. They are used as second-line or later therapy after immunotherapy ± chemotherapy.

Reference: Cancer Council Australia – 2021 – Lung Cancer OCP; TGA – 2024 – Sotorasib Approval