Treatment of Advanced or Metastatic NSCLC with KRAS G12C Mutation

This protocol addresses the first-line management of patients with advanced or metastatic non-small cell lung cancer (NSCLC) harbouring a KRAS G12C mutation — a molecularly defined subgroup with specific treatment considerations.

Clinical Scenario

KRAS G12C is an activating mutation found in approximately 25% of patients with adenocarcinomas in North American populations. Its presence defines this subgroup and shapes the selection of first-line systemic therapy.

Treatment Approach

First-line therapy selection is guided by PD-L1 expression level, directing the use of immunotherapy and/or platinum-based chemotherapy. Notably, KRAS-targeted therapies are not part of the first-line approach in this setting. The full regimen selection algorithm, including threshold-based options and sequencing, is available in the complete protocol →

Instant Access to Structured Evidence-Based Regimens

References

KRAS G12C is an activating mutation that results in activation of downstream oncogenic pathways.

Data suggest that approximately 25% of patients with adenocarcinomas in a North American population have a KRAS mutation.

The Panel recommends using PD-L1 expression level to guide selection of first-line systemic therapy regimen (such as immunotherapy and/or chemotherapy) for patients with advanced or metastatic NSCLC with KRAS G12C mutations.

KRAS-targeted therapies are not recommended as first-line treatment options for advanced or metastatic NSCLC with a KRAS G12C mutation.

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