Comparative efficacy and safety of immune checkpoint inhibitor-related therapies for advanced melanoma: a Bayesian network analysis.

Oncotarget

Department of Molecular Biology, College of Basic Medical Sciences, Norman Bethune Health Science Center, Jilin University, Changchun 130021, China.

Published: October 2017

AI Article Synopsis

  • The study compared the efficacy and safety of nine immune checkpoint inhibitor therapies for advanced melanoma in a cohort of 5,413 patients across twelve trials.
  • Ipilimumab plus nivolumab, nivolumab, and pembrolizumab showed significant improvements in progression-free survival (PFS) compared to ipilimumab and other combinations, while ibalimumab plus gp100 was the least effective.
  • Nivolumab and pembrolizumab demonstrated the best overall survival (OS) outcomes with fewer adverse effects, positioning them as optimal treatment options, whereas the combination of ipilimumab plus nivolumab, although effective for PFS, was linked to higher toxicity.

Article 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663542PMC
http://dx.doi.org/10.18632/oncotarget.18906DOI Listing

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