Martin Reck1, Alexander Luft1, Judith Balmañà1, Libor Havel1, Sang-We Kim1, Wallace Akerley1, M. Catherine Pietanza1, Yi‐Long Wu1, Christoph Zielinski1, Michael J. Thomas1, Enriqueta Felip1, Kathryn A. Gold1, Leora Horn1, Joachim G.J.V. Aerts1, Kazuhiko Nakagawa1, Paul Lorigan1, Anne Pieters1, Teresa Kong Sanchez1, Justin Fairchild1, David R. Spigel1
1Martin Reck, LungenClinic Grosshansdorf, Airway Research Center North, Grosshansdorf; Michael Thomas, Translational Lung Research Center Heidelberg, Thoraxklinik im Universitätsklinikum Heidelberg, Heidelberg, Germany; Alexander Luft, Leningrad Regional Clinical Hospital, Leningrad, Russia; Aleksandra Szczesna, Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy w Otwocku, Otwocku, Poland; Libor Havel, Hospital Na Bulovce, Prague, Czech Republic; Sang-We Kim, Asan Medical Center and University of Ulsan...
Tóm tắt
PurposePatients with extensive-stage disease small-cell lung cancer (SCLC) have poor survival outcomes despite first-line chemotherapy with etoposide and platinum. This randomized, double-blind phase III study evaluated the efficacy and safety of ipilimumab or placebo plus etoposide and platinum in patients with newly diagnosed extensive-stage disease SCLC.Patients and MethodsPatients were randomly assigned at a ratio of one to one to receive chemotherapy with etoposide and platinum (cisplatin or carboplatin) plus ipilimumab 10 mg/kg or placebo every 3 weeks for a total of four doses each in a phased induction schedule (chemotherapy in cycles one to four; ipilimumab or placebo beginning in cycle three up to cycle six), followed by ipilimumab or placebo maintenance every 12 weeks. Primary end point was overall survival (OS) among patients receiving at least one dose of blinded study therapy.ResultsOf 1,132 patients randomly assigned, 954 received at least one dose of study therapy (chemotherapy plus ipilimumab, n = 478; chemotherapy plus placebo, n = 476). Median OS was 11.0 months for chemotherapy plus ipilimumab versus 10.9 months for chemotherapy plus placebo (hazard ratio, 0.94; 95% CI, 0.81 to 1.09; P = .3775). Median progression-free survival was 4.6 months for chemotherapy plus ipilimumab versus 4.4 months for chemotherapy plus placebo (hazard ratio, 0.85; 95% CI, 0.75 to 0.97). Rates and severity of treatment-related adverse events were similar between arms, except for diarrhea, rash, and colitis, which were more frequent with chemotherapy plus ipilimumab. Rate of treatment-related discontinuation was higher with chemotherapy plus ipilimumab (18% v 2% with chemotherapy plus placebo). Five treatment-related deaths occurred with chemotherapy plus ipilimumab and two with chemotherapy plus placebo.ConclusionAddition of ipilimumab to chemotherapy did not prolong OS versus chemotherapy alone in patients with newly diagnosed extensive-stage disease SCLC. No new or unexpected adverse events were observed with chemotherapy plus ipilimumab. Several ongoing studies are evaluating ipilimumab in combination with programmed death-1 inhibitors in SCLC.
