A systematic review and network meta-analysis of immunotherapy and targeted therapy for advanced melanoma

Joao Paulo da Silveira Nogueira Lima, Mina Georgieva, Benjamin Haaland, Gilberto de Lima Lopes

Research output: Contribution to journalArticle

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.

LanguageEnglish (US)
Pages1143-1153
Number of pages11
JournalCancer Medicine
Volume6
Issue number6
DOIs
StatePublished - Jun 1 2017
Externally publishedYes

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Immunotherapy
Melanoma
Mitogen-Activated Protein Kinase Kinases
Disease-Free Survival
Therapeutics
Survival
Odds Ratio
Network Meta-Analysis
Patient Selection
Survival Rate
Randomized Controlled Trials
Biomarkers
Databases
Pharmaceutical Preparations

Keywords

  • Bayesian
  • biomarker
  • BRAF
  • immunotherapy
  • melanoma
  • meta-analysis

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

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. DOI: 10.1002/cam4.1001

A systematic review and network meta-analysis of immunotherapy and targeted therapy for advanced melanoma. / da Silveira Nogueira Lima, Joao Paulo; Georgieva, Mina; Haaland, Benjamin; de Lima Lopes, Gilberto.

In: Cancer Medicine, Vol. 6, No. 6, 01.06.2017, p. 1143-1153.

Research output: Contribution to journalArticle

da Silveira Nogueira Lima, JP, 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, vol 6, no. 6, pp. 1143-1153. DOI: 10.1002/cam4.1001
da Silveira Nogueira Lima JP, Georgieva M, Haaland B, de Lima Lopes G. A systematic review and network meta-analysis of immunotherapy and targeted therapy for advanced melanoma. Cancer Medicine. 2017 Jun 1;6(6):1143-1153. Available from, DOI: 10.1002/cam4.1001
da Silveira Nogueira Lima, Joao Paulo ; Georgieva, Mina ; Haaland, Benjamin ; de Lima Lopes, Gilberto. / A systematic review and network meta-analysis of immunotherapy and targeted therapy for advanced melanoma. In: Cancer Medicine. 2017 ; Vol. 6, No. 6. pp. 1143-1153
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