A Randomized Phase 2 Trial of Nivolumab Versus Nivolumab-Ipilimumab Combination in EGFR-Mutant NSCLC.

Although immune checkpoint inhibitors (ICIs) have dramatically improved outcomes for nononcogene-addicted NSCLC, monotherapy with programmed cell death protein-1 (PD1) inhibition has been associated with low efficacy in the EGFR-mutant setting. Given the potential for synergism with combination checkpoint blockade, we designed a trial to test the activity of combination nivolumab (N)-ipilimumab (NI) in EGFR-mutant NSCLC. This is a randomized phase 2 study (NCT03091491) of N versus NI combination in EGFR tyrosine kinase inhibitor (TKI)-resistant NSCLC, with crossover permitted on disease progression. The primary end point was the objective response rate, and the secondary end points included progression-free survival, overall survival, and safety of ICI after EGFR TKI. Recruitment ceased owing to futility after 31 of 184 planned patients were treated. A total of 15 patients received N and 16 received NI combination. There were 16 patients (51.6%) who had programmed death-ligand (PDL1) 1 greater than or equal to 1%, and 15 (45.2%) harbored Immune checkpoint inhibition is ineffective in EGFR TKI-resistant NSCLC. Whereas a small subgroup of EGFR-mutant NSCLC may be immunogenic and responsive to ICI, better biomarkers are needed to select appropriate patients.

Informations de copyright

© 2022 by the International Association for the Study of Lung Cancer.