Oncodrivers in Advanced or Metastatic NSCLC: Current and Future Standards of Care - Episode 2
Evaluating Efficacy Outcomes of TKI Therapies in KRAS G12C-Mutated NSCLC
Panelists discuss how 2 FDA-approved KRAS G12C inhibitors (adagrasib and sotorasib) perform in second-line therapy after immunotherapy and chemotherapy, with both showing improved progression-free survival versus docetaxel despite modest gains, leading to their adoption as standard of care due to better tolerability profiles.
Second-Line KRAS G12C Inhibitors: Adagrasib and Sotorasib
Two FDA-approved KRAS G12C inhibitors are currently available for second-line treatment: adagrasib and sotorasib. The CodeBreak 200 study demonstrated sotorasib's efficacy versus docetaxel in postplatinum therapy, showing progression-free survival improvements of 5.6 versus 4.5 months. However, the study did not achieve statistical significance for overall survival, highlighting the challenges of surpassing docetaxel's established efficacy in second-line non–small cell lung cancer (NSCLC) treatment.
Adagrasib showed promising results in the KRYSTAL-1 study, leading to FDA approval based on comprehensive clinical data. Both KRAS G12C inhibitors offer significant advantages over traditional chemotherapy, including oral administration, improved tolerability profiles, and superior patient-reported outcomes. The convenience of home-based oral therapy represents a substantial quality of life improvement compared to intravenous docetaxel administration.
Clinical practice has rapidly adopted KRAS G12C inhibitors as standard second-line therapy for appropriate patients. The favorable toxicity profiles and ease of administration make these targeted agents preferable to chemotherapy in the postplatinum, post–checkpoint inhibitor setting. Patient selection focuses on molecular confirmation of KRAS G12C mutations through comprehensive genomic profiling, emphasizing the critical role of precision diagnostics in modern oncology practice.
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