Nivolumab with or without ipilimumab as maintenance therapy after first-line chemotherapy failed to prolong survival among patients with extensive-disease small cell lung cancer (ED-SCLC), according to the results of the CheckMate 451 trial published in the Journal of Clinical Oncology.
Although most patients with ED-SCLC respond to first-line chemotherapy, recurrence is common. Previous studies of maintenance cytotoxic or targeted therapy have not reported improved survival. The aim of this study was to determine if maintenance therapy with combined immune checkpoint inhibitors could improve survival in patients with ED-SLCL.
The double-blind, phase 3 CheckMate 451 trial (ClinicalTrials.gov Identifier: NCT0538666) randomly assigned 834 patients with ED-SCLC to nivolumab plus ipilimumab, nivolumab monotherapy, or placebo for up to 2 years. All patients had no disease progression after up to 4 cycles of first-line chemotherapy. The primary endpoint was overall survival.
The median age at baseline was 64 years, 36% of patients were women, and 93% were current or former smokers. The majority of patients had a partial response or stable disease after first-line chemotherapy. Of the patients evaluated for programmed death-ligand 1 (PD-L1) status, 46% had expression of 1% or higher.
Overall survival was found to be similar among all groups, with a median of 9.2 months with nivolumab/ipilimumab, 10.4 months with nivolumab alone, and 9.6 months with placebo (hazard ratio [HR], 0.84; 95% CI, 0.69-1.02).
Progression-free survival was longer with immune checkpoint inhibition. Median progression-free survival was 1.4 months with placebo compared with 1.7 months with nivolumab/ipilimumab (HR, 0.72; 95% CI, 0.60-0.87) and 1.9 months with nivolumab (HR, 0.67; 95% CI, 0.56-0.81).
Objective response rates (ORR) were also higher with immune checkpoint inhibition. The ORR was 9.1% with the combination, 11.5% with nivolumab monotherapy, and 4.2% with placebo. The median duration of response was 10.2 and 11.2 months with nivolumab/ipilimumab and nivolumab monotherapy, respectively, compared with 8.1 months with placebo.
Adverse events and serious adverse events occurred more frequently with nivolumab/ipilimumab and led to discontinuation among 28.8% of patients. Adverse events led to discontinuation of nivolumab among 7.9% of patients and 0.4% of patients in the placebo group.
The authors concluded that “maintenance with combination therapy in the current dosing regimen did not prolong [overall survival] in patients with ED-SCLC after first-line platinum-based chemotherapy.”
Owonikoko TK, Park K, Govindan R, et al. Nivolumab and ipilimumab as maintenance therapy in extensive-disease small-cell lung cancer: CheckMate 451. J Clin Oncol. Published online March 8, 2021. doi:10.1200/JCO.20.02212