Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial

Ipilimumab, an anti-CTLA4 monoclonal antibody, demonstrated survival benefit in melanoma with immune-related (ir) adverse events (irAEs) managed by the protocol-defined guidelines. This phase 2 study evaluated ipilimumab + paclitaxel (Taxol)/carboplatin in extensive-disease-small-cell lung cancer (ED-SCLC). Patients (n = 130) with chemotherapy-naive ED-SCLC were randomized 1: 1: 1 to receive paclitaxel (175 mg/m(2))/carboplatin (area under the curve = 6) with either placebo (control) or ipilimumab 10 mg/kg in two alternative regimens, concurrent ipilimumab (ipilimumab + paclitaxel/carboplatin followed by placebo + paclitaxel/carboplatin) or phased ipilimumab (placebo + paclitaxel/carboplatin followed by ipilimumab + paclitaxel/carboplatin). Treatment was administered every 3 weeks for a maximum of 18 weeks (induction), followed by maintenance ipilimumab or placebo every 12 weeks. End points included progression-free survival (PFS), irPFS, best overall response rate (BORR); irBORR, overall survival (OS), and safety. Phased ipilimumab, but not concurrent ipilimumab, improved irPFS versus control [HR (hazard ratio) = 0.64; P = 0.03]. No improvement in PFS (HR = 0.93; P = 0.37) or OS (HR = 0.75; P = 0.13) occurred. Phased ipilimumab, concurrent ipilimumab and control, respectively, were associated with median irPFS of 6.4, 5.7 and 5.3 months; median PFS of 5.2, 3.9 and 5.2 months; median OS of 12.9, 9.1 and 9.9 months. Overall rates of grade 3/4 irAEs were 17, 21 and 9% for phased ipilimumab, concurrent ipilimumab and control, respectively. These results suggest further investigation of ipilimumab in ED-SCLC.