A randomized phase II study of bevacizumab in combination with docetaxel or S-1 in patients with non-squamous non-small-cell lung cancer previously treated with platinum based chemotherapy (HANSHIN Oncology Group 0110)

Objectives This randomized phase II trial investigated the efficacy and safety of docetaxel plus bevacizumab and S-1 plus bevacizumab in the second-line treatment of non-squamous (non-Sq) non-small-cell lung cancer (NSCLC). Materials and methods Patients with non-Sq NSCLC who experienced disease progression after prior platinum-based chemotherapy with or without bevacizumab were randomly assigned to receive docetaxel plus bevacizumab (DB) once every 3 weeks or S-1 orally twice daily on days 1–14 plus bevacizumab (SB) on day 1 every 3 weeks until disease progression. Results Ninety patients were randomized. The median progression-free survival (PFS) was 3.9 months (95% confidence interval [CI] = 3.0–6.5) in DB and 3.5 months (95% CI = 2.9–5.9) in SB. The objective response rate was significantly higher in DB than in SB (22.2% vs. 2.2%; P = 0.004), whereas the disease control rates of the arms were identical (62.2% vs. 62.2%; P = 1.00). Patients receiving DB were more likely to have ≥grade 3 neutropenia (93.4% vs. 4.4%) and febrile neutropenia (33.3% vs. 0%) than SB. In DB, PFS and overall survival (OS) were significantly longer among bevacizumab-naïve patients than among bevacizumab-experienced patients (median PFS: 7.2 vs. 2.9 months; P = 0.004; and median OS: 21.3 vs. 14.1 months; P = 0.012). Conclusion DB and SB produced modest PFS benefits in the second-line treatment of patients with advanced non-Sq NSCLC. Because of the toxicity of DB and the low response rate of SB, neither regimen warrants further investigation, excluding DB in bevacizumab-naïve patients with advanced non-Sq NSCLC.