KRYSTAL-1: Review of Key Efficacy Data

Opinion
Video

An overview of the role of KRAS G12C inhibitors in the second line and beyond for KRAS G12C mutated NSCLCs after progression on platinum-based chemotherapy.

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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