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.