Kras Mutations As Predictive Biomarker In Patients With Egfr Wild-Type Stage Iv Nonsquamous Non-Small Cell Lung Cancer (Nsclc) Recruited In A Phase Ii Clinical Study With Carboplatin-Docetaxel-Bevacizumab.

e18069 Background: KRAS mutation are harbored in ~30% of NSCLC patients, and have been described associated with an upregulation of genes involved in angiogenesis, including vascular endothelial growth factor/vascular permeability factor (VEGF/VPF). Bevacizumab (BVZ) is a recombinant monoclonal humanized antibody targeted against VEGF and added to carboplatin-paclitaxel chemotherapy has demonstrated to improve outcome in non-squamous NSCLC. The objectives of this study were to analyze the impact of KRAS mutations in response rate (RR) and time to progression (TTP) in a cohort of patients homogeneously treated with BVZ in combination with carboplatin-docetaxel. Methods: Patients treated with up to 6 cycles of carboplatin (AUC 5), docetaxel (75 mg/m2) and BVZ (7.5 mg/kg) on day 1, every 21 days. Patients with RR or stable disease continued maintenance BVZ (7.5 mg/kg) every 21 days until disease progression. KRAS mutations at codons 12, 13 and 61 were analyzed by COBAS KRAS Mutation Test (Roche) from DNA purified from diagnostic samples. Results: 30 patients were enrolled (24 male, 6 female); median age was 62 years (range 44-82); ECOG 1/2: 22/8. 27 were adenocarcinomas and 3, undifferentiated large cell carcinoma. Smoking habit: 1 non-smoker, 16 current-smoker, and 13 former-smoker. Seven patients were KRAS mutated (23.3%). Carboplatin-docetaxel-bevacizumab therapy showed a significant improved efficacy in KRAS wild-type compared to mutated patients (RR: 85.7% vs 14.3%, p=0.045; and TTP: 9.38 months vs 7.46 months, p=0.033), but did not impact on overall survival (12.4 months in wild type vs 11.06 months in KRAS mutated, p= 0.780). Conclusions: KRAS mutations predict RR and TTP in wild-type EGFR stage IV non-squamous NSCLC patients treated with bevacizumab-based therapy.