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Clin Cancer Res. 2016 Feb 15;22(4):886-94. doi: 10.1158/1078-0432.CCR-15-1136. Epub 2015 Oct 7.

Nivolumab in Resected and Unresectable Metastatic Melanoma: Characteristics of Immune-Related Adverse Events and Association with Outcomes.

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Department of Graduate Medical Education, University of South Florida, Tampa, Florida.
Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida.
Clinical Trials Office, Moffitt Cancer Center, Tampa, Florida.
Department of Cutaneous Oncology, Lombardi Comprehensive Cancer Center, Washington, DC.
Donald A. Adam Comprehensive Melanoma Research Center, Moffitt Cancer Center, Tampa, Florida.



Retrospective analysis of irAEs in melanoma patients treated with nivolumab.


Data were pooled from 148 patients (33 resected, 115 unresectable) treated with nivolumab plus peptide vaccine or nivolumab alone every 2 weeks for 12 weeks. Patients with stable disease or regression received an additional 12-week cycle, then nivolumab alone every 12 weeks for up to 2 additional years. Frequency, grade, and characteristics of immune-related adverse events (irAE) were analyzed. A 12-week landmark survival analysis using a multivariate time-dependent Cox proportional hazard model assessed difference in overall survival (OS) in the presence or absence of irAEs.


IrAEs of any grade were observed in 68.2% of patients (101 of 148). Grade III/IV irAEs were infrequent: 3 (2%) had grade III rash, 2 (1.35%) had asymptomatic grade III elevation in amylase/lipase, and 2 (1.35%) had grade III colitis. A statistically significant OS difference was noted among patients with any grade of irAE versus those without (P ≤ 0.001), and OS benefit was noted in patients who reported three or more irAE events (P ≤ 0.001). Subset analyses showed statistically significant OS differences with rash [P = 0.001; HR, 0.423; 95% confidence interval (CI), 0.243-0.735] and vitiligo (P = 0.012; HR, 0.184; 95% CI, 0.036-0.94). Rash and vitiligo also correlated with statistically significant OS differences in patients with metastatic disease (P = 0.004 and P = 0.028, respectively). No significant survival differences were seen with other irAEs (endocrinopathies, colitis, or pneumonitis).


Cutaneous irAEs are associated with improved survival in melanoma patients treated with nivolumab, and clinical benefit should be validated in larger prospective analyses.

[Indexed for MEDLINE]
Free PMC Article

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