Strategies for monitoring and mitigating hepatotoxicity with KRAS G12C inhibitors

EP: 1.An overview on KRAS+ mutated lung adenocarcinoma

EP: 2.Selecting Frontline Therapy for KRAS+ mutated lung adenocarcinoma

EP: 3.KRYSTAL-1: Review of Key Efficacy Data

EP: 4.Comparing the Efficacy and Safety of KRAS G12C inhibitors for patients with NSCLC

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EP: 5.Strategies for monitoring and mitigating hepatotoxicity with KRAS G12C inhibitors

EP: 6.Key Considerations for Treating patients with NSCLC using KRAS inhibitors

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.