Efficacy and safety of nivolumab and ipilimumab with or without chemotherapy for unresectable non-small cell lung cancer: a multicenter retrospective observational study.

Introduction: Compared to platinum-based therapies, a combination of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) has demonstrated improved outcomes in advanced non-small cell lung cancer (NSCLC), albeit with higher rates of immune-related adverse events (irAEs). This multicenter retrospective study evaluated the efficacy and safety of nivolumab and ipilimumab with or without chemotherapy (NI and NICT) in real-world clinical settings.

Methods: We enrolled 215 treatment-naïve NSCLC patients who received NI or NICT between December 2020 and May 2023 at 14 institutions in Japan. Severe irAEs (Grade ≥ 3) were assessed using the Common Terminology Criteria for Adverse Events. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier methods and propensity score matching.

Results: Of 215 patients, 104 and 111 received NI and NICT, respectively. The median PFS was 5.3 and 5.9 months for NI and NICT, respectively. The median OS was 22.1 and 19.2 months for NI and NICT, respectively. High fever within 3 weeks of treatment initiation and high tumor burden were indicators of severe irAEs. Grade 3 or higher irAEs occurred in 36.5% patients in the NI group and 50.5% patients in the NICT group, with higher treatment-related mortality in the NICT group (5.4% vs. 1.9% in NI).

Conclusions: NI and NICT showed comparable efficacies in PFS and OS. However, NICT had a higher incidence of severe irAEs and treatment-related mortality. High tumor burden and early high fever were predictors of severe irAEs. Further research is warranted to optimize the efficacy and safety of NICT for NSCLC treatment.