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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.

Author information

1
Department of Graduate Medical Education, University of South Florida, Tampa, Florida. morganna.freemankeller@moffitt.org.
2
Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida.
3
Clinical Trials Office, Moffitt Cancer Center, Tampa, Florida.
4
Department of Cutaneous Oncology, Lombardi Comprehensive Cancer Center, Washington, DC.
5
Donald A. Adam Comprehensive Melanoma Research Center, Moffitt Cancer Center, Tampa, Florida.

Abstract

PURPOSE:

Retrospective analysis of irAEs in melanoma patients treated with nivolumab.

EXPERIMENTAL DESIGN:

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.

RESULTS:

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).

CONCLUSIONS:

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

PMID:
26446948
PMCID:
PMC4755809
DOI:
10.1158/1078-0432.CCR-15-1136
[Indexed for MEDLINE]
Free PMC Article

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