Oncodrivers in Advanced or Metastatic NSCLC: Current and Future Standards of Care - Episode 1
KRAS G12C-Mutated NSCLC: Current Treatment Paradigms
Panelists discuss how critical broad-panel next-generation sequencing is for all patients with non–small cell lung cancer to enable biomarker-guided treatment, with focus on KRAS G12C mutations found in 12% to 14% of patients and consideration of PD-L1 expression levels and comutations when selecting frontline therapy.
Introduction and KRAS G12C Mutations in NSCLC
This medical discussion focuses on targeted therapeutic approaches for advanced non–small cell lung cancer (NSCLC), specifically examining KRAS and ROS1 pathways. The discussion emphasizes the critical importance of comprehensive next-generation sequencing for all NSCLC patients to enable proper biomarker testing and targeted therapy matching. Without adequate molecular profiling, patients cannot access potentially lifesaving targeted treatments.
KRAS mutations represent approximately 30% of NSCLC cases, with KRAS G12C comprising 12% to 14% of all non–small cell lung cancer diagnoses. Treatment decisions for KRAS G12C–positive patients depend heavily on PD-L1 expression levels, with single-agent immunotherapy recommended for patients with PD-L1 expression ≥50%, while combination immunotherapy plus chemotherapy is preferred for those with PD-L1 <50%. Comutations, particularly STK11/LKB1, may influence treatment selection toward dual checkpoint blockade strategies.
The evolving landscape of KRAS G12C targeted therapy represents a significant advancement in precision oncology for lung cancer patients. Current treatment algorithms integrate biomarker testing results with patient characteristics to optimize therapeutic outcomes. The discussion highlights how molecular profiling has transformed treatment approaches, moving from broad chemotherapy regimens to personalized targeted interventions based on specific genetic alterations.
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