Phase 1b study of ramucirumab in combination with irinotecan plus cisplatin in chemo-naïve patients with extensive-stage small-cell lung cancer

Previous studies have shown the potentials of anti-angiogenesis inhibitors in extensive-stage small-cell lung cancer (SCLC). This single-institutional phase 1b study aimed to determine the recommended dose of ramucirumab (anti-vascular endothelial growth factor receptor-2 antibody) in combination with irinotecan plus cisplatin for extensive-stage SCLC.Chemo-naïve patients with extensive-stage SCLC were enrolled and received ramucirumab (day 1 and 15) with irinotecan (60 mg/m2, day 1, 8, and 15) plus cisplatin (60 mg/m2, day 1) every 4 weeks for four cycles, followed by biweekly maintenance ramucirumab. The recommended ramucirumab dose (10 or 8 mg/kg) was determined using a traditional 3 + 3 design, and the number of patients treated at the recommended dose was set at 10 to evaluate drug efficacy and tolerability (UMIN000032671).The first 3 patients that received irinotecan plus cisplatin with ramucirumab 10 mg/kg did not experience dose-limiting toxicities. Thus, the recommended dose of ramucirumab was set at 10 mg/kg, and 10 patients received this dose. The objective response rate was 100% (95% CI, 69-100%), with a median progression-free survival of 7.2 months (95% CI, 5.3-9.0) and median overall survival of 22.4 months (95% CI, 12.1-not reached). Grade 3 neutropenia and hypertension were observed in 4 and 2 patients, respectively. No ramucirumab-related deaths were noted; hypertension and bleeding events were observed in 5 and 6 patients, respectively.This study showed the satisfactory tolerability and efficacy of ramucirumab at 10 mg/kg in combination with irinotecan plus cisplatin in chemo-naïve patients with extensive-stage SCLC.