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KRAS mutations affect prognosis of non-small-cell lung cancer patients treated with first-line platinum containing chemotherapy

2015; Impact Journals LLC; Volume: 6; Issue: 32 Linguagem: Inglês

10.18632/oncotarget.5607

1949-2553

Mirko Marabese, Monica Ganzinelli, Marina Chiara Garassino, Frances A. Shepherd, Sheila Piva, Elisa Caiola, Marianna Macerelli, Anna Bettini, Calogero Lauricella, Irene Floriani, Gabriella Farina, Flavia Longo, Lucia Bonomi, Agnese Fabbri, Silvio Veronese, Silvia Marsoni, Massimo Broggini, Eliana Rulli,

Cancer therapeutics and mechanisms

// Mirko Marabese 1,* , Monica Ganzinelli 2,* , Marina C. Garassino 2 , Frances A. Shepherd 3 , Sheila Piva 4 , Elisa Caiola 1 , Marianna Macerelli 2 , Anna Bettini 5 , Calogero Lauricella 6 , Irene Floriani 1 , Gabriella Farina 4 , Flavia Longo 7 , Lucia Bonomi 5 , M. Agnese Fabbri 8 , Silvio Veronese 6 , Silvia Marsoni 9 , Massimo Broggini 1 and Eliana Rulli 1 1 Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy 2 Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 3 Princess Margaret Cancer Center, University of Toronto, Toronto, Canada 4 Oncology Department, Ospedale Fatebenefratelli e Oftalmico, Milan, Italy 5 Oncology Department, Ospedale Papa Giovanni XXIII, Bergamo, Italy 6 Molecular Pathology Unit, Niguarda Cancer Center, Ospedale Niguarda Ca' Granda, Milan, Italy 7 Medical Oncology, Policlinico Umberto I, Rome, Italy 8 Ospedale Belcolle, Viterbo, Italy 9 Clinical Trials Coordination Unit, Institute for Cancer Research and Treatment, IRCCS, Candiolo, Italy * These authors equally contributed to this work Correspondence to: Massimo Broggini, email: // Marina C. Garassino, email: // Keywords : KRAS, NSCLC, platinum, first-line Received : May 04, 2015 Accepted : August 26, 2015 Published : September 15, 2015 Abstract KRAS mutations seem to indicate a poor outcome in Non-Small-Cell Lung Cancer (NSCLC) but such evidence is still debated. The aim of this planned ancillary study within the TAILOR trial was to assess the prognostic value of KRAS mutations in advanced NSCLC patients treated with platinum-based first-line chemotherapy. Patients ( N = 540), enrolled in the study in 52 Italian hospitals, were centrally genotyped twice in two independent laboratories for EGFR and KRAS mutational status. Of these, 247 patients were eligible and included in the present study. The primary endpoint was overall survival (OS) according to KRAS mutational status in patients harboring EGFR wild-type. Sixty (24.3%) out of 247 patients harbored KRAS mutations. Median OS was 14.3 months and 10.6 months in wild-type and mutated KRAS patients, respectively (unadjusted Hazard Ratio [HR]=1.41, 95%Confidence Interval [CI]: 1.03-1.94 P = 0.032; adjusted HR=1.39, 95%CI: 1.00-1.94 P = 0.050). This study, with all consecutive patients genotyped, indicates that the presence of KRAS mutations has a mild negative impact on OS in advanced NSCLC patient treated with a first-line platinum-containing regimen. Trial Registration:clinicaltrials.gov identifierNCT00637910