2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.12C.03 Toxicities Associated with Immune Checkpoint Inhibitors Followed by KRAS G12C Inhibitors in Patients with Metastatic NSCLC

EP.12C.03 Toxicities Associated with Immune Checkpoint Inhibitors Followed by KRAS G12C Inhibitors in Patients with Metastatic NSCLC

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This study investigates the toxicity profile of sequential treatment involving immune checkpoint inhibitors (ICIs) followed by KRAS G12C inhibitors in patients with metastatic non-small cell lung cancer (NSCLC). The primary focus was on hepatotoxicity and pneumonitis risk associated with this treatment sequence. <br /><br />A retrospective analysis of electronic medical records was conducted at a single center, involving 28 patients who received KRAS G12C inhibitors as a second or later line of treatment between June 2021 and November 2023. Of these, 23 patients had prior exposure to ICIs before receiving KRAS G12C inhibitors like sotorasib. Patients were categorized based on the timing of ICI exposure: within 3 months, beyond 3 months, or no prior exposure.<br /><br />Results showed that 50% of patients who received ICIs within 3 months prior to the KRAS G12C inhibitors experienced some degree of hepatotoxicity, specifically transaminitis. Notably, 25% experienced severe (Grade 3) transaminitis, leading to dose adjustments or treatment discontinuation in some cases. Comparatively, those with no or later ICI exposure exhibited lower hepatotoxicity rates, with no incidents of Grade 3 transaminitis. Only one case of Grade 3 pneumonitis was reported, occurring in a patient who had ICI exposure within 3 months.<br /><br />The study concludes that the combination treatment poses a significant risk of hepatotoxicity, particularly when KRAS G12C inhibitors are administered within 3 months following ICI therapy. The risk of pneumonitis, however, was considerably lower. Further research is needed to better understand the mechanisms and optimize treatment timing to mitigate these adverse effects. This research indicates the importance of cautious sequencing and timing in the administration of these therapies to minimize potential toxicities.

Asset Subtitle

Sana Kagalwalla

Meta Tag

Speaker Sana Kagalwalla

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

immune checkpoint inhibitors

KRAS G12C inhibitors

metastatic non-small cell lung cancer

hepatotoxicity

pneumonitis

transaminitis

treatment sequencing

adverse effects

dose adjustments

retrospective analysis