Final Results of a Phase II Study of Bevacizumab, Cisplatin and Pemetrexed as First-Line Therapy for Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer

Abstract

Background: Efficacy and safety data for cisplatin and pemetrexed plus bevacizumabinnon squamousnon non-small cell lung cancer (NSCLC) are still limited. Nevertheless, either bevacizumab plus platinum doublet or pemetrexed plus platinum is approved options for first line therapy. Predictive factors for bevacizumab are needed. KRAS is one of the most common oncogenic drivers in lung cancer. Its prognostic and predictive value in NSCLC is under investigation. Patients and methods: This trial evaluates the addition of bevacizumab 7.5 mg/kg to cisplatin 75 mg/m 2 plus pemetrexed 500 mg/m 2 as first line treatment in stage IV non-squamous NSCLC patients. Maintenance bevacizumab was received as monotherapy until progressive disease, unacceptable toxicityor consent with drawal. The primary objective was progression free survival (PFS). Secondary objectives included overall survival (OS), safety, global objective responses and the determination of KRAS mutation at baseline. Results: From March 2009 to March 2012, 31 patients were enrolled. Mean age was 59.19 (standard deviation (SD) 8.53). From all the patients included in this trial, 67.70% were men. KRAS was wild type in 19 patients (58.06%); in 7 (22.58%) was mutated and was unknown in 6 patients (19.35%). Median PFS for KRAS mutated patients was 4 months, whereas for the KRAS wild type it was 7.9 months (P = 0.0031). Median OS was 4 months for the KRAS population, and 16.1 months for the KRAS wild type (P = 0.0032). Twenty four patients (77.42%) experienced at least a grade 3 - 4 adverse event. The most common grade 3 - 4 toxicity was asthenia. Conclusions: Both PFS and OS were statistically longer for the KRAS wild type patients compared with the KRAS mutated population (P = 0.0031). Median OS was shorter than the reported in previous trials with bevacizumab. Nevertheless, focussing on the OS for KRAS wild type patients, this achieves a result or 16.1 months. Therefore, this would be a consistent data supporting to qualify this parameter as a predictive factor before starting treatment for NSCLC.