Please use this identifier to cite or link to this item: https://doi.org/10.1002/cam4.1001
Title: A systematic review and network meta-analysis of immunotherapy and targeted therapy for advanced melanoma
Authors: da Silveira Nogueira Lima, J.P
Georgieva, M
Haaland, B 
de Lima Lopes, G
Keywords: B Raf kinase
carboplatin
cobimetinib
cytotoxic T lymphocyte antigen 4
dabrafenib
dacarbazine
ipilimumab
mitogen activated protein kinase
nivolumab
paclitaxel
pembrolizumab
placebo
programmed death 1 ligand 1
selumetinib
temozolomide
ticilimumab
trametinib
vemurafenib
immunological antineoplastic agent
Article
cancer immunotherapy
dosage schedule comparison
drug dose comparison
drug efficacy
gene mutation
human
melanoma
meta analysis
molecularly targeted therapy
overall survival
priority journal
progression free survival
qualitative analysis
randomized controlled trial (topic)
systematic review
disease free survival
immunotherapy
melanoma
treatment outcome
Antineoplastic Agents, Immunological
Disease-Free Survival
Humans
Immunotherapy
Melanoma
Molecular Targeted Therapy
Randomized Controlled Trials as Topic
Treatment Outcome
Issue Date: 2017
Citation: da Silveira Nogueira Lima, J.P, Georgieva, M, Haaland, B, de Lima Lopes, G (2017). A systematic review and network meta-analysis of immunotherapy and targeted therapy for advanced melanoma. Cancer Medicine 6 (6) : 1143-1153. ScholarBank@NUS Repository. https://doi.org/10.1002/cam4.1001
Rights: Attribution 4.0 International
Abstract: Immune and BRAF-targeted therapies have changed the therapeutic scenario of advanced melanoma, turning the clinical decision-making a challenging task. This Bayesian network meta-analysis assesses the role of immunotherapies and targeted therapies for advanced melanoma. We retrieved randomized controlled trials testing immune, BRAF- or MEK-targeted therapies for advanced melanoma from electronic databases. A Bayesian network model compared therapies using hazard ratio (HR) for overall survival (OS), progression-free survival (PFS), and odds ratio (OR) for response rate (RR), along with 95% credible intervals (95% CrI), and probabilities of drugs outperforming others. We assessed the impact of PD-L1 expression on immunotherapy efficacy. Sixteen studies evaluating eight therapies in 6849 patients were analyzed. For OS, BRAF-MEK combination and PD-1 single agent ranked similarly and outperformed all other treatments. For PFS, BRAF-MEK combination surpassed all other options, including CTLA-4-PD-1 dual blockade hazard ratio (HR: 0.56; 95% CrI: 0.33–0.97; probability better 96.2%), whereas BRAF single agent ranked close to CTLA-4-PD-1 blockade. For RR, BRAF-MEK combination was superior to all treatments including CTLA-4-PD-1 (OR: 2.78; 1.18–6.30; probability better 97.1%). No OS data were available for CTLA-4-PD-1 blockade at the time of systematic review, although PFS and RR results suggested that this combination could also bring meaningful benefit. PD-L1 expression, as presently defined, failed to inform patient selection to PD-1-based immunotherapy. BRAF-MEK combination seemed an optimal therapy for BRAF-mutated patients, whereas PD-1 inhibitors seemed optimal for BRAF wild-type patients. Longer follow-up is needed to ascertain the role of CTLA-4-PD-1 blockade. Immunotherapy biomarkers remain as an unmet need. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Source Title: Cancer Medicine
URI: https://scholarbank.nus.edu.sg/handle/10635/178675
ISSN: 20457634
DOI: 10.1002/cam4.1001
Rights: Attribution 4.0 International
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