A phase II, multicenter evaluation of docetaxel, gemcitabine, and bevacizumab followed by bevacizumab alone in patients with locally advanced or metastatic non-small cell lung cancer (central localization excluded)

Abstract

19077 Background: Platinum-based doublets are the standard of care for advanced and metastatic NSCLC; however many patients (pts) can not tolerate side effects of this combination. This study was designed to evaluate the efficacy and tolerability of Docetaxel + Gemcitabine in combination with Bevacizumab (D/G/B) in chemotherapy-naïve Stage IIIB(non-pleural effusion)/IV NSCLC pts. Methods: Newly diagnosed pts (> 18y) with histologically proven NSCLC (squamous cell excluded) and ECOG PS ≤ 2 were assigned to receive D/G/B: G -1000 mg/m2 IV over 0.5 hour on Days 1 and 8; D -75 mg/m2 IV over 1 hour on Day 8; and B -15 mg/kg IV on Day 1 over 21 day cycles, for 6 cycles maximum. Response was evaluated after every 2 treatment cycles (i.e. after Cycles 2, 4, and 6). Subjects with responding and stable disease (i.e., SD, PR, or CR) received bevacizumab 15 mg/kg IV every 21 days after completion of chemotherapy to complete 1 year of treatment, or until discontinuation. The primary endpoint for this study was PFS. Secondary endpoints included safety of the combination drugs, evaluation of treatment-related toxicities, tumor response rate, and overall survival. Results: A total of17 pts were enrolled; of the 17 pts in the safety population, 6 (35.3%) were male, 10 (58.8%) < 65y, 14 (82.4%) had an ECOG PS score 0 or 1; 16 (94.1%) had Stage IV disease. Mean ± SD number of cycles completed was 3.6 ± 3.06 (range 1–10). As of September 24, 2007, five deaths have been reported, three due to disease progression, two due to gastrointestinal perforation (GIP). One pt who died of disease progression had also experienced a GIP. The investigators and the sponsor agreed to close this study based on the reported incidence of GIP. Review of world-wide trials containing the D/G/B regimen confirmed an incidence of GIPs lower than the incidence reported in this trial. Conclusions: Additional safety (patients with GIP safety reports will be summarized) and efficacy data will be presented. The use of bevacizumab in combination with chemotherapy regimens in advanced NSCLC should be limited to controlled Ph II/III clinical trials until an acceptable safety profile is established. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis