Oncodrivers in Advanced or Metastatic NSCLC: Current and Future Standards of Care - Episode 3
Panelists discuss how KRAS G12C inhibitors differentiate in their toxicity profiles, with sotorasib carrying higher hepatotoxicity risk especially post–checkpoint inhibitor therapy, while adagrasib shows more gastrointestinal toxicities, and the importance of washout periods to mitigate liver toxicity.
Toxicity Profiles and Management of KRAS G12C Inhibitors
KRAS G12C inhibitors share common toxicity patterns typical of oral anti-cancer agents, including gastrointestinal effects such as nausea, vomiting, and diarrhea. Liver function abnormalities represent a significant concern requiring careful monitoring and potential dose modifications. The toxicity profiles differ between agents, with sotorasib carrying higher hepatotoxicity risk, particularly following checkpoint inhibitor therapy, while adagrasib demonstrates increased gastrointestinal toxicity rates.
Hepatotoxicity management requires careful consideration of prior immunotherapy exposure and appropriate washout periods. Clinical experience suggests that longer intervals between checkpoint inhibitor completion and KRAS inhibitor initiation may reduce hepatotoxicity rates. Some patients who experience liver toxicity with one KRAS G12C inhibitor may tolerate alternative agents, providing important sequencing options for clinical management.
Practical toxicity management involves frequent liver function monitoring, especially in patients with recent checkpoint inhibitor exposure. When disease progression necessitates immediate treatment initiation without adequate washout periods, enhanced monitoring protocols help ensure patient safety. The relatively short half-lives of KRAS G12C inhibitors allow for rapid resolution of toxicities upon treatment holds, facilitating effective toxicity management strategies in clinical practice.