The pathbreaking discovery of sotorasib as KRAS G12C inhibitor has revolutionized the prognostic outcome of KRAS mutated metastatic NSCLC. This is a single centre experience of KRAS mutated NSCLC in an Indian cohort, underscoring the unmet urgent need of sotorasib in this part of the world.
Among the 3899 NSCLC patients registered between 2016 to 2020, 163 patients were tested for KRAS alterations, of which 50 patients were confirmed to harbor a KRAS variant by molecular testing. Appropriate statistical analysis was done to compare G12C and non-G12C subtypes, including their survival outcomes.
Median age was 63 years (range: 36-81years) with a preponderance of non-G12C mutations in both sexes. Smokers were higher in G12C group (16 vs 4 pts, p=0.09). G12C group showed lesser PDL1 expression (>1%) than non-G12C group (13 vs. 15 pts, p=0.09). Molecular analysis revealed 3 main types of KRAS mutations: G12C, G12V and G12D in 17 (34%), 9(18%) and 6 (12%) pts respectively. None of them had KRAS complex mutations. The co-mutations predominantly detected included TP53 in 7 (14%), STK11 in 3 (6%), FGFR4 in 4 (8%), PIK3CA, EGFR and ALK in 2 cases each, BRAF and CTNNB1 in 1 case each. Co-mutations were significantly more frequent in the non-G12C group (p<0.05). 36 patients received chemotherapy and rest were lost to follow up. The median PFS and OS of the entire cohort on chemotherapy were 5.4 months (mo) and 11.1 mo respectively. The median PFS and OS of G12C vs non-G12C groups were 6.4 mo (95% CI: 2.8-11.8) vs 3.8 mo (95%CI: 2.9-7.7) and 15.2 mo (95% CI: 9.8-17.2) vs 16.1 mo (95% CI: 10.7-19.3) respectively. With a median follow-up of 14.3 mo, both PFS and OS were not statistically significant between the groups, p=0.08 and 0.20 respectively.
This is by far the largest experience from India of KRAS mutated NSCLC, comparing G12C with other KRAS mutants. Despite limitations of retrospective nature, small sample size, heterogeneity in the cohort and missing data points, and limited molecular profiling this study is relevant in the light of approval of targeted therapy, sotorasib, which is currently unavailable in this country.
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