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Non-G12C KRAS — SCE Medical Oncology MCQ

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HardLung CancerNon-G12C KRASSCE Medical Oncology

A 55-year-old woman with NSCLC has molecular profiling showing a KRASG12D mutation. Unlike KRASG12C, what is the current treatment landscape for non-G12C KRAS mutations?

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Correct answer: E — No approved targeted therapies exist for non-G12C KRAS mutations (G12D, G12V, G13D) — these patients are treated with standard immunochemotherapy; KRAS G12D-specific inhibitors are in early clinical trials

KRAS G12C is currently the only directly druggable KRAS mutation (sotorasib, adagrasib). Other common KRAS mutations (G12D ~14%, G12V ~8%, G13D) have no approved targeted therapies yet. KRAS G12D inhibitors (MRTX1133 and others) are in early-phase clinical trials. Non-G12C KRAS-mutant NSCLC is treated with standard PD-L1-guided immunochemotherapy. SHP2 inhibitors and SOS1 inhibitors are being evaluated as pan-KRAS approaches. This highlights the mutation-specific nature of KRAS targeting.

Reference: ESMO 2024 NSCLC; Jänne et al NEJM 2022; Hallin et al Cancer Discov 2022