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- Title
Canadian Consensus Recommendations on the Management of KRAS G12C-Mutated NSCLC.
- Authors
Cheema, Parneet K.; Banerji, Shantanu O.; Blais, Normand; Chu, Quincy S.-C.; Juergens, Rosalyn A.; Leighl, Natasha B.; Sacher, Adrian; Sheffield, Brandon S.; Snow, Stephanie; Vincent, Mark; Wheatley-Price, Paul F.; Yip, Stephen; Melosky, Barbara L.
- Abstract
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.
- Subjects
CANADA; CANADA. Health Canada; RAS oncogenes; PEMETREXED; NON-small-cell lung carcinoma; IMMUNE checkpoint inhibitors
- Publication
Current Oncology, 2023, Vol 30, Issue 7, p6473
- ISSN
1198-0052
- Publication type
Article
- DOI
10.3390/curroncol30070476