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

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

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.

Keywords: KRAS; NSCLC; first-line; platinum.

Conflict of interest statement

CONFLICTS OF INTRESTS

The authors have declared no conflicts of interest.

Figures

Figure 1. Patient CONSORT diagram
Figure 1. Patient CONSORT diagram
Figure 2. Kaplan-Meier curves for survival
Figure 2. Kaplan-Meier curves for survival
Curves for overall survival (A) and progression free survival (B) according to the KRAS status.
Figure 3. Kaplan Meier curves for survival
Figure 3. Kaplan Meier curves for survival
Curves for overall survival A. and progression free survival B. according to the main different types of mutations (G12C, G12D, G12V).

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Source: PubMed

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