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JAMA Oncol. 2018 Mar 1;4(3):374-378. doi: 10.1001/jamaoncol.2017.2925.

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

Author information

1
Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan.
2
Clinical Research Center, Kindai University Hospital, Osaka-Sayama, Japan.
3
Department of Medical Oncology and Respiratory Medicine, National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Japan.
4
Department of Medical Oncology, Kishiwada City Hospital, Kishiwada, Japan.
5
Department of Medical Oncology, Izumi Municipal Hospital, Izumi, Japan.

Abstract

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.

PMID:
28975219
PMCID:
PMC6583041
DOI:
10.1001/jamaoncol.2017.2925
[Indexed for MEDLINE]
Free PMC Article

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