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Published on: September 20, 2016
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KRAS G12C in advanced NSCLC: Prevalence, co-mutations, and testing
Tony Kiat Hon Lim1, Ferdinandos Skoulidis2, Keith M Kerr3
1Division of Pathology, Singapore General Hospital, Singapore.
Lung Cancer (Amsterdam, Netherlands)
|September 8, 2023
Summary
KRAS G12C is a key target in non-small cell lung cancer (NSCLC). Testing for this mutation is crucial for guiding treatment decisions, especially with new targeted therapies available.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- KRAS mutations are common in advanced non-squamous non-small cell lung cancer (NSCLC).
- KRAS G12C is the most frequent KRAS variant, making it a significant therapeutic target.
- The development of KRAS G12C-selective inhibitors has shifted KRAS from a prognostic to a predictive biomarker.
Purpose of the Study:
- To review the evolving role of KRAS G12C in advanced NSCLC.
- To discuss KRAS G12C biology, prevalence, co-mutations, and molecular testing strategies.
- To highlight the clinical relevance of KRAS G12C testing for treatment decisions.
Main Methods:
- Literature review of KRAS G12C in advanced NSCLC.
- Analysis of real-world prevalence data across different geographic regions.
- Examination of clinical data on KRAS G12C co-mutations (STK11, KEAP1, TP53).
Main Results:
- Significant geographic variations in KRAS G12C prevalence were observed.
- KRAS G12C-mutant NSCLC frequently co-occurs with STK11, KEAP1, and TP53 mutations.
- Sotorasib and adagrasib are approved for second-line treatment, emphasizing early testing.
Conclusions:
- KRAS G12C testing should be integrated into routine biomarker assessment before first-line therapy.
- Next-generation sequencing is recommended for comprehensive biomarker analysis.
- Molecular testing results are essential for guiding treatment strategies in KRAS G12C-mutated NSCLC.
