Abstract
BACKGROUND: The combination of nivolumab and ipilimumab, which act on different immune checkpoint molecules, is a promising first-line treatment strategy for advanced nonsmall cell lung cancer (NSCLC). However, real-world clinical data on this regimen, particularly regarding the relationship between adverse events (AEs) and efficacy, are inadequate. METHODS: This real-world retrospective study was conducted on patients with advanced or recurrent NSCLC treated using a combination of nivolumab and ipilimumab as a first-line treatment. We extracted the data of consecutive eligible patients from four institutions in Japan between December 2020 and November 2022. RESULTS: The study population comprised 184 patients who received nivolumab plus ipilimumab (median follow up period: 13.0 months [0.3-35.0]). In total, 81.0% (n = 149) of the patients were men, and the median age was 72.0 years (range: 46-80). The median progression-free survival (PFS) and overall survival (OS) were 6.6 months (95% confidence interval [CI]: 4.7-8.2) and 17.4 months (95% CI: 11.9-20.4), respectively. Skin disorders, liver dysfunction, thyroid dysfunction, and pneumonitis were the most common adverse events (AEs), with AEs occurring in 154 patients (83.7%). The median PFS in the AE group was longer than that in the non-AE group (8.2 vs. 2.6 months, p < 0.0001). The median OS in the AE group was also better than that in the non-AE group (19.3 vs. 6.1 months, p < 0.0001). Multivariate logistic regression analysis identified smoking history and high PD-L1 expression as factors related to the incidence of grade 3 and 4 AEs, respectively. The incidence of multiple AEs revealed a significant association with a longer PFS and OS. Skin disorders, adrenal insufficiency, and eosinophilia were the AEs with the greatest impact on survival. CONCLUSIONS: Patients who experienced AEs had significantly longer PFS. Among AEs, the occurrence of skin disorders, adrenal insufficiency, and eosinophilia were likely to prolong PFS and OS.