An Exploratory Randomized Phase II Trial Comparing CDDP Plus S-1 With Bevacizumab and CDDP Plus Pemetrexed With Bevacizumab Against Patients With Advanced Non-squamous Non-small Cell Lung Cancer

Background/Aim: It remains unclear which chemotherapeutic regimens are better for the addition of bevacizumab. We conducted an exploratory randomized phase II trial comparing first-line S-1 plus cisplatin with bevacizumab and pemetrexed plus cisplatin with bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC). Patients and Methods: Chemotherapy-naive patients received S-1 (80 mg/m(2)) from day 1 to day 14 plus cisplatin (80 mg/m(2)) on day 1 with bevacizumab (15 mg/kg) on day 1, followed by maintenance with bevacizumab plus S-1 (SCB) on day 1 every 3 weeks and pemetrexed (500 mg/m(2)) on day 1 plus cisplatin (75 mg/m(2)) on day 1 with bevacizumab (15 mg/kg) on day 1 followed by maintenance bevacizumab plus pemetrexed (PCB) on day 1 every 3 weeks. The expression of thymidylate synthase (TS) was analyzed using immunohistochemistry. Results: Forty-eight patients were enrolled in this study, and eligible patients were randomly assigned at 1:1 ratio to receive SCB (n=24) or PCB (n=24). The median number of chemotherapy and maintenance therapy for SCB and PCB was 4 (range, 1-6 cycles) and 4 (range, 2-6 cycles), and 5 (range, 0-39 cycles) and 5 (range, 0-28 cycles), respectively. The overall response rate (ORR) for PCB and SCB were 54.2% and 83.3%, respectively (p=0.06). The median progression-free survival (PFS) and overall survival (OS) for PCB and SCB were 406 and 351 days, (p=0.96), and 678 and 1190 days, respectively (p=0.23). The mild adverse events were observed in both regimens. TS expression was more predictive of the chemotherapeutic response in SCB compared to PCB, but not for PFS. Conclusion: The combination regimen of SCB was identified as having a similar activity and tolerability to that of PCB in patients with advanced non-squamous NSCLC.