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J Clin Oncol. 2016 Nov 1;34(31):3740-3748. doi: 10.1200/JCO.2016.67.6601.

Phase III Randomized Trial of Ipilimumab Plus Etoposide and Platinum Versus Placebo Plus Etoposide and Platinum in Extensive-Stage Small-Cell Lung Cancer.

Author information

1
Martin 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 College of Medicine, Seoul, Korea; Wallace Akerley, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Maria Catherine Pietanza, Memorial Sloan Kettering Cancer Center, New York, NY; Kathryn Gold, University of Texas MD Anderson Cancer Center, Houston, TX; Leora Horn, Vanderbilt-Ingram Cancer Center; David Spigel, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Anne Pieters, Teresa Kong Sanchez, and Justin Fairchild, Bristol-Myers Squibb, Princeton, NJ; Yi-long Wu, Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong, People's Republic of China; Christoph Zielinski, Medical University of Vienna, Vienna, Austria; Enriqueta Felip, Vall d'Hebron University Hospital, Barcelona, Spain; Joachim Aerts, Erasmus MC Cancer Institute, Rotterdam, the Netherlands; Kazuhiko Nakagawa, Kinki University Hospital, Osaka, Japan; and Paul Lorigan, the Christie NHS Foundation Trust, Manchester, United Kingdom.

Abstract

Purpose Patients 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 Methods Patients 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. Results Of 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. Conclusion Addition 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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01450761.

PMID:
27458307
DOI:
10.1200/JCO.2016.67.6601
[Indexed for MEDLINE]

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