KRAS mutation is present in almost 33% of NSCLC patients. Retrospective trials have shown a tendency of higher efficacy of ICI in this subgroup, and prospective trials with KRAS inhibitors are emerging. If KRAS could take part as a biomarker score for ICI or KRAS inhibitors efficacy is still unknown.
A retrospective analysis was done in our center, from all NSCLC patients with either tissue DNA and/or ctDNA NGS analyses, treated with schemes including ICI. NGS methods included: Oncomine V3.0, Guardant 360, and Foundation liquid.
Two hundred one patients had NGS done with 51(25.4%) with KRAS mutation detected. Median age was 62 years old, and 53% had PDL1 >1%, within 21% with >=50%. High CD8 T Cell infiltration was detected in 18% but was unknown in 51%. KRAS most frequent mutations detected were G12C (43,9%) and G12D (17,1%). TP53 co-mutation was present in 29% (KP group), NF1 in 11.3% and STK11 in 9,7% (KL group). Most KRAS G12C, had PDL1 positive (69%) and 25% had PDL1 >=50%. TILs infitration in 25% with high infiltration KL group had PDL1 positive in 20% (anyone with PDL1 50%) and without CD8 T-cell infiltration. A combination of chemo-immunotherapy (anti-PDL1) was administered in 26% of all, and chemotherapy monotherapy in 53%. Patients KRASmut and PDL1 positive, showed better median OS than PDL1 negative (28 vs 21,9 months, p=0,25), and those with PDL1 >=50% expression reached median survival of 39 months. Patients KRASmut and PDL1 negative, obtained similar low survival rates regardless of treatment (OS 15%). In KP group, PDL1 negative showed mOS of 12 months compared to 21 months if PDL1 positive. Survival was lower in STK11mut respect to STK11wt (17 vs 24,8 months). In KL group, treatment did not affect survival (mOS 10 months). Globally, more than one co-mutation tended to worse survival (14 months).
Our sample represents general NSCLC patients. KP group shows an immune phenotype (high PDL1, CD8 Tcells infiltration) and better survival rates for ICI included therapy. KL group is a challenging group without real ICI efficacy and results from KRAS inhibitors early trials have shown major benefit in this group. Our study shows a potential molecular score to select treatment. A wider sample is expected to support this observation.
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All authors have declared no conflicts of interest.