KRAS-specific Amino Acid Substitutions are Associated With Different Responses to Chemotherapy in Advanced Non–small-cell Lung Cancer

Emerging evidence is highlighting different behaviors of non-small-cell lung cancer according to KRAS amino acid substitutions (AAS). We have shown that, in a large sample of 1190 patients, response to chemotherapy differs according to KRAS AAS in non-small-cell lung cancer. This supports the use of different chemotherapy regimens according to KRAS AAS. Background: Emerging data highlight different clinical behaviors according to KRAS amino acid substitutions (AASs) in patients with non-small-cell lung cancer (NSCLC). We aimed to evaluate whether different KRAS AASs were associated with different responses to chemotherapy. Patients and Methods: We retrospectively reviewed data from 1190 patients with KRAS mutations who underwent first-line platinum-based chemotherapy for stage IV NSCLC. The response to different chemotherapy regimens was evaluated using the Response Evaluation Criteria In Solid Tumors criteria (v 1.1). Overall survival and time to progression (TTP) were secondary endpoints. Results: Taxane was associated with the best response in the entire cohort (odds ratio, 2.52; 95% confidence interval [CI], 1.82-3.48; P < .001), especially in G12V patients (odds ratio, 2.15; 95% CI, 1.05-4.41; P = .036). Taxane was associated with improved TTP in the entire cohort (hazard ratio [HR), 0.31; 95% CI, 0.26-0.38; P < .001), especially in G13D patients (HR, 0.47; 95% CI, 0.22-1.01; P =.054). Pemetrexed was associated with the worst TTP in the entire cohort, particularly in G12V patients, who had the worst response rates (HR, 0.55; 95% CI, 0.30-0.99; P = .049). No impact on overall survival was observed according to different chemotherapy regimens and AASs. Conclusion: KRAS-specific AAS appears to induce different responses to chemotherapy regimens after first-line platinum-based chemotherapy in advanced NSCLC. (C) 2018 Elsevier Inc. All rights reserved.