Abstract

Abstract Introduction: K-Ras mutation is thought to be related with poor outcome of NSCLC patients with an advanced stage of disease. The role of K-Ras mutation as a predictor of response for these patients treated only with chemotherapy is poorly understood. Patients and methods: From a retrospective database from 2 university hospitals all patients with advanced stage, nonsquamous, NSCLC treated with palliative platinum containing chemotherapy were selected. Patients were included when archive tumour tissue was available for DNA extraction. High resolution melting followed by PCR sequencing was performed for KRAS exon1 and 2. Response to treatment was assessed by RECIST. The databases were matched by treatment. Results: A total of 179 patients were included in this study. All patients were treated with chemotherapy and were no candidate for treatment with curative intent. There were 59 patients with a K-Ras mutation (32.9%). There was no significant difference in basic characteristics between the group with a K-Ras mutation and the group with K-Ras wild-type. Mean age 59 years (range 32–83 years), 108 males and 71 females. ECOG performance score 0/1/2/3 73/77/13/2. Thirty patients with stage IIIb disease, 149 patients with stage IV disease. Progression as best response to treatment was reported in 21/59 patients with a K-ras mutation (35.6%) and 34/120 patients (28.3%) with a K-Ras wild type, this was not significant (p=0.611). The median progression free survival (PFS) in the group with a K-Ras mutation was 4.1 months (95% CI 3.12–5.0 months) compared to 5.4 months (95% CI 4.4–6.4 months) in patients with K-Ras wild type (p=0.202). The overall survival (OS) in the group with a K-Ras mutation, was 8.3 months (95% CI 5.2–11.4 months) compared to 12.5 months (95% CI 10.2–14–7 months) in patients with K-Ras wild type (p=0.037). Conclusion: In our series K-Ras mutation was not predictive for response to platinum containing chemotherapy in patients with advanced NSCLC. K-Ras mutational status was prognostic for overall survival.

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