Current Oncology (Jul 2023)

Canadian Consensus Recommendations on the Management of KRAS G12C-Mutated NSCLC

  • Parneet K. Cheema,
  • Shantanu O. Banerji,
  • Normand Blais,
  • Quincy S.-C. Chu,
  • Rosalyn A. Juergens,
  • Natasha B. Leighl,
  • Adrian Sacher,
  • Brandon S. Sheffield,
  • Stephanie Snow,
  • Mark Vincent,
  • Paul F. Wheatley-Price,
  • Stephen Yip,
  • Barbara L. Melosky

DOI
https://doi.org/10.3390/curroncol30070476
Journal volume & issue
Vol. 30, no. 7
pp. 6473 – 6496

Abstract

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Activating mutations in Kirsten rat sarcoma viral oncogene homologue (KRAS), in particular, a point mutation leading to a glycine-to-cysteine substitution at codon 12 (G12C), are among the most frequent genomic alterations in non-small cell lung cancer (NSCLC). Several agents targeting KRAS G12C have recently entered clinical development. Sotorasib, a first-in-class specific small molecule that irreversibly inhibits KRAS G12C, has since obtained Health Canada approval. The emergence of novel KRAS-targeted therapies warrants the development of evidence-based consensus recommendations to help clinicians better understand and contextualize the available data. A Canadian expert panel was convened to define the key clinical questions, review recent evidence, and discuss and agree on recommendations for the treatment of advanced KRAS G12C-mutated NSCLC. The panel agreed that testing for KRAS G12C should be performed as part of a comprehensive panel that includes current standard-of-care biomarkers. Sotorasib, the only approved KRAS G12C inhibitor in Canada, is recommended for patients with advanced KRAS G12C-mutated NSCLC who progressed on guideline-recommended first-line standard of care for advanced NSCLC without driver alterations (immune-checkpoint inhibitor(s) [ICIs] +/− chemotherapy). Sotorasib could also be offered as second-line therapy to patients who progressed on ICI monotherapy that are not candidates for a platinum doublet and those that received first-line chemotherapy with a contraindication to ICIs. Preliminary data indicate the activity of KRAS G12C inhibitors in brain metastases; however, the evidence is insufficient to make specific recommendations. Regular liver function monitoring is recommended when patients are prescribed KRAS G12C inhibitors due to risk of hepatotoxicity.

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