KRAS-specific Amino Acid Substitutions are Associated With Different Responses to Chemotherapy in Advanced Non-small-cell Lung Cancer.
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.
['Renaud|Stéphane|S|', 'Guerrera|Francesco|F|', 'Seitlinger|Joseph|J|', 'Reeb|Jérémie|J|', 'Voegeli|Anne-Claire|AC|', 'Legrain|Michèle|M|', 'Mennecier|Bertrand|B|', 'Santelmo|Nicola|N|', 'Falcoz|Pierre-Emmanuel|PE|', 'Quoix|Elisabeth|E|', 'Chenard|Marie-Pierre|MP|', 'Weingertner|Noëlle|N|', 'Beau-Faller|Michèle|M|', 'Massard|Gilbert|G|']
D000368:Aged D000970:Antineoplastic Agents D054316:Biomarkers, Pharmacological D001952:Bridged-Ring Compounds D002289:Carcinoma, Non-Small-Cell Lung D015331:Cohort Studies D004252:DNA Mutational Analysis D005260:Female D006801:Humans D008175:Lung Neoplasms D008297:Male D008875:Middle Aged D009154:Mutation D009367:Neoplasm Staging D000068437:Pemetrexed D016283:Proto-Oncogene Proteins p21(ras) D012189:Retrospective Studies D016019:Survival Analysis D043823:Taxoids
Response Chemotherapy Lung cancer KRAS Amino-acid substitution