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 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.

Ann Oncol. 2012 Aug 2;

Authors: Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Lu H, Cuillerot JM, Lynch TJ

Abstract
BackgroundIpilimumab, 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).DesignPatients (n�=�130) with chemotherapy-na�ve 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.ResultsPhased 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.ConclusionThese results suggest further investigation of ipilimumab in ED-SCLC.

PMID: 22858559 [PubMed - as supplied by publisher]

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