No Benefit From Adding Ipilimumab To Second-Line Nivolumab For Advanced Squamous NSCL

Author: By Lynda Williams, Senior medwireNews Reporter

medwireNews: The Lung-MAP S1400I trial has failed to demonstrate improved overall survival (OS) by combining nivolumab with ipilimumab for patients with stage IV squamous non-small-cell lung (NSCLC) lung cancer who have previously received platinum-doublet chemotherapy.

After a median 29.5 months of follow-up, median OS in the phase III, open-label study was 10 months for the 125 patients who were randomly assigned to receive nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks until disease progression or intolerable toxicity.

This did not significantly differ from the median OS of 11 months achieved by the 127 patients who received only nivolumab, report Scott Gettinger, from Yale Cancer Center in New Haven, Connecticut, USA, and co-workers.

The combination and nivolumab-only treatment groups were also comparable for the secondary endpoints of investigator-assessed progression-free survival (median 3.8 vs 2.9 months) and response rate (18 vs 17%).

Patients given nivolumab plus ipilimumab did have a longer median duration of response, at 28.4 months versus just 9.7 months with nivolumab alone, although the latter duration rose to 13.2 months when six unconfirmed partial responses to nivolumab were excluded from the analysis.

Subgroup analysis showed that tumour PD-L1 expression of at least 5% or a tumour mutational burden (TMB) of 10 mutations/Mb or higher was not significantly associated with OS within either treatment group.

Among patients with a TMB above 10 mutations/Mb there was a trend towards better OS with nivolumab plus ipilimumab versus nivolumab alone regardless of PD-L1 tumour expression status. But for patients with a TMB less than 10 mutations/Mb and a PD-L1 tumour expression of less than 1%, receipt of combination treatment showed a trend towards poorer OS compared with nivolumab alone.

However, the researchers emphasize that the “exploratory nature” of these analyses and the small number of patients in each subgroup must “limit conclusions.”

A similar proportion of patients in the combination and nivolumab-only arms experienced grade 3 or more severe treatment-related adverse events (39.5 vs 33.3%), with immune-related adverse events of any severity reported in 66.0% and 59.0%, respectively.

Treatment discontinuation for toxicity occurred in 25% of the combination and 15% of the monotherapy groups, the team reports in JAMA Oncology.

Scott Gettinger and co-authors note that several trials are now investigating nivolumab plus ipilimumab as a salvage therapy for advanced NSCLC patients who have progressed after first-line PD-1 pathway inhibitor therapy.

“These studies enroll both patients with acquired and primary resistance to PD-1 axis inhibitor therapy”, they explain.

“Until these studies and others are completed, there will continue to be no role for combination therapy with nivolumab and ipilimumab in patients with pretreated advanced NSCLC.”

Reference

Gettinger SN, Redman MW, Bazhenova L, et al. Nivolumab plus ipilimumab vs nivolumab for previously treated patients with stage IV squamous cell lung cancer. The Lung-MAP S1400I phase 3 randomized clinical trial. JAMA Oncol; Advance online publication 15 July 2021. doi:10.1001/jamaoncol.2021.2209