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

• Published in: Annals of oncology Vol. 24; no. 1; pp. 75 - 83
• Main Authors: Reck, M., Bondarenko, I., Luft, A., Serwatowski, P., Barlesi, F., Chacko, R., Sebastian, M., Lu, H., Cuillerot, J.-M., Lynch, T.J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2013
• Subjects: Antibodies, Monoclonal - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carboplatin - administration & dosage; combination therapy; Double-Blind Method; first-line treatment; Humans; Ipilimumab; Lung Neoplasms - drug therapy; Paclitaxel - administration & dosage; paclitaxel/carboplatin; Placebos; randomized phase 2 trial; small-cell lung cancer; combination therapy; first-line treatment; paclitaxel/carboplatin; randomized phase 2 trial; small-cell lung cancer; ipilimumab
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mds213

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-naïve ED-SCLC were randomized 1: 1: 1 to receive paclitaxel (175mg/m2)/carboplatin (area under the curve=6) with either placebo (control) or ipilimumab 10mg/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.