Strategies for monitoring and mitigating hepatotoxicity with KRAS G12C inhibitors


An overview of recognizing and managing common immune-related and systemic adverse events with immune checkpoint inhibitors, chemotherapy and KRAS targeted therapies in NSCLC.

Case: A 64-year-old male diagnosed with a KRAS G12C mutated stage IV adenocarcinoma

Clinical Presentation:

  • A 64-year-old male presents with cough and fatigue
  • PMH: hyperlipidemia (well controlled with simvastatin), GERD (takes Omeprazole)
  • SH: married with 2 grown children who live in other states; 30 pack-year smoking history; no family history of cancer.

Initial Clinical Workup and Diagnosis:

  • CT chest showed right upper lobe lung mass with contralateral lung nodules concerning metastases.
  • PET/CT revealed additional metastases in the liver.
  • Molecular Testing: KRAS G12C mutation
  • Staging: IV adenocarcinoma; ECOG PS 1

Initial Treatments:

  • Patient was initiated on carboplatin-pemetrexed + pembrolizumab.
    • Good initial response after 4 cycles but progressed after 8 months.

Disease Progression and Subsequent Treatments:

  • Experienced disease progression after 8 months of carboplatin-pemetrexed + pembrolizumab, notably growth in hepatic metastases
    • Confirmed progression on CT and PET/CT scans
  • After progression on initial chemo+IO, molecular testing confirmed retained KRAS G12C mutation.
    • The patient then started on second-line therapy with the adagrasib.
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