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Brief Report
March 2018

Association of Immune-Related Adverse Events With Nivolumab Efficacy in Non–Small-Cell Lung Cancer

Author Affiliations
  • 1Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
  • 2Clinical Research Center, Kindai University Hospital, Osaka-Sayama, Japan
  • 3Department of Medical Oncology and Respiratory Medicine, National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Japan
  • 4Department of Medical Oncology, Kishiwada City Hospital, Kishiwada, Japan
  • 5Department of Medical Oncology, Izumi Municipal Hospital, Izumi, Japan
JAMA Oncol. 2018;4(3):374-378. doi:10.1001/jamaoncol.2017.2925
Key Points

Question  Are immune-related adverse events associated with outcome of nivolumab treatment in patients with non–small-cell lung cancer (NSCLC)?

Findings  In this multi-institutional medical record review including 134 patients with advanced or recurrent NSCLC treated with nivolumab monotherapy, landmark and multivariable analyses showed that immune-related adverse events were significantly associated with a better treatment outcome.

Meaning  Early recognition and proper management of immune-related adverse events are important to maximize the therapeutic benefit of immune-checkpoint inhibitors in patients with NSCLC.


Importance  Immune-related adverse events (irAEs) have been associated with the efficacy of PD-1 (programmed cell death protein 1) inhibitors in patients with melanoma, but whether such an association exists for non–small-cell lung cancer (NSCLC) has remained unknown.

Objective  To evaluate the relation of irAEs to nivolumab efficacy in NSCLC.

Design, Setting, and Participants  In this study based on landmark and multivariable analyses, a total of 134 patients with advanced or recurrent NSCLC who were treated with nivolumab in the second-line setting or later between December 2015 and August 2016 were identified from a review of medical records from multiple institutions, including a university hospital and community hospitals. Data were updated as of December 31, 2016.

Exposures  The absence or presence of any irAE before the landmark date.

Main Outcomes and Measures  Kaplan-Meier curves of progression-free survival (PFS) according to the development of irAEs in 6-week landmark analysis were evaluated with the log-rank test as a preplanned primary objective. Overall survival (OS) was similarly evaluated. Multivariable analysis of both PFS and OS was performed with Cox proportional hazard regression models.

Results  In a cohort of 134 patients (median [range] age, 68 [33-85] years; 90 men [67%], 44 women [33%]), irAEs were observed in 69 of the 134 study patients (51%), including 12 patients (9%) with such events of grade 3 or 4, and 24 patients (18%) requiring systemic corticosteroid therapy. In 6-week landmark analysis, median PFS was 9.2 months (95% CI, 4.4 to not reached [NR]) and 4.8 months (95% CI, 3.0 to 7.5) (P = .04) whereas median OS was NR (95% CI, 12.3 to NR) and 11.1 months (95% CI, 9.6 to NR) (P = .01) for patients with or without irAEs, respectively. Multivariable analysis also revealed that irAEs were positively associated with survival outcome, with hazard ratios of 0.525 (95% CI, 0.287 to 0.937; P = .03) for PFS and 0.282 (95% CI, 0.101 to 0.667; P = .003) for OS.

Conclusions and Relevance  Development of irAEs was associated with survival outcome of nivolumab treatment in patients with advanced or recurrent NSCLC. Further studies are needed to confirm our findings.