Research Papers:
Comparative efficacy and safety of immune checkpoint inhibitor-related therapies for advanced melanoma: a Bayesian network analysis
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Abstract
Xin Li1,*, Junpeng Wang2,*, Yun Yao1, Lei Yang1, Zhiqin Li3, Cheng Yu4, Peiyan Zhao1, Yongli Yu3 and Liying Wang1
1Department of Molecular Biology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun 130021, China
2Department of Urology, Henan Provincial People’s Hospital, Zhengzhou 450003, China
3Department of Immunology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun 130021, China
4Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China
*These authors have contributed equally to this work
Correspondence to:
Liying Wang, email: [email protected]
Yongli Yu, email: [email protected]
Keywords: immune checkpoint inhibitor, therapy, efficacy, safety, advanced melanoma
Received: February 14, 2017 Accepted: April 19, 2017 Published: July 01, 2017
ABSTRACT
Objectives: We aimed to compare and rank the effects of 9 immune checkpoint inhibitor-related therapies for treating advanced melanoma.
Methods: We searched Pubmed, Cochrane databases, Web of Science, and ClinicalTrials.gov for randomized controlled trials of the immune checkpoint inhibitor-related treatments for advanced melanoma. Analysis was done on a Bayesian framework.
Results: Twelve trials including 5413 patients were identified. Ipilimumab plus nivolumab, nivolumab, and pembrolizumab were significantly more efficacious for progression-free survival (PFS) than ipilimumab (hazard ratio [HR], 0.38, 0.50, and 0.58, respectively), ipilimumab plus chemotherapy (0.45, 0.60, and 0.70, respectively), or ipilimumab plus sargramostim (0.44, 0.57, and 0.67, respectively). Ipilimumab plus gp100 was significantly less efficacious for PFS than the remaining eight immune checkpoint inhibitor-related strategies. Pembrolizumab was significantly more efficacious than ipilimumab and ipilimumab plus gp100 (HR, 0.66, and 0.64, respectively) in improving overall survival (OS). Nivolumab significantly improved OS over tremelimumab (HR, 0.48). Ipilimumab plus sargramostim was ranked the second most effective strategy in terms of OS and well tolerated. Nivolumab and pembrolizumab showed the best profile of acceptability, with significantly less high-grade adverse events than ipilimumab (odds ratio [OR], 0.49 and 0.50, respectively), tremelimumab (0.21 and 0.21, respectively), ipilimumab plus chemotherapy (0.13 and 0.13, respectively), or ipilimumab plus nivolumab (0.15 and 0.15, respectively).
Conclusions: Nivolumab, pembrolizumab and ipilimumab plus sargramostim might be optimum treatments for advanced melanoma because they have the most favorable balance between benefits and acceptability. Ipilimumab plus nivolumab is the most effective in prolonging PFS, but is far more toxic than nivolumab and pembrolizumab.
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