A systematic literature review and network meta-analysis of effectiveness and safety outcomes in advanced melanoma.

A systematic literature review and network meta-analysis of effectiveness and safety outcomes in advanced melanoma.

Publication date: Dec 01, 2019

Although a myriad of novel treatments entered the treatment paradigm for advanced melanoma, there is lack of head-to-head evidence. We conducted a network meta-analysis (NMA) to estimate each treatment’s relative effectiveness and safety.

A systematic literature review (SLR) was conducted in Embase, MEDLINE and Cochrane to identify all phase III randomised controlled trials (RCTs) with a time frame from January 1, 2010 to March 11, 2019. We retrieved evidence on treatment-related grade III/IV adverse events, progression-free survival (PFS) and overall survival (OS). Evidence was synthesised using a Bayesian fixed-effect NMA. Reference treatment was dacarbazine. In accordance with RCTs, dacarbazine was pooled with temozolomide, paclitaxel and paclitaxel plus carboplatin. To increase homogeneity of the study populations, RCTs were only included if patients were not previously treated with novel treatments.

The SLR identified 28 phase III RCTs involving 14,376 patients. Nineteen and seventeen treatments were included in the effectiveness and safety NMA, respectively. For PFS, dabrafenib plus trametinib (hazard ratio [HR] PFS: 0.21) and vemurafenib plus cobimetinib (HR PFS: 0.22) were identified as most favourable treatments. Both had, however, less favourable safety profiles. Five other treatments closely followed (dabrafenib [HR PFS: 0.30], nivolumab plus ipilimumab [HR PFS: 0.34], vemurafenib [HR PFS: 0.38], nivolumab [HR PFS: 0.42] and pembrolizumab [HR PFS: 0.46]). In contrast, for OS, nivolumab plus ipilimumab (HR OS: 0.39), nivolumab (HR OS: 0.46) and pembrolizumab (HR OS: 0.50) were more favourable than dabrafenib plus trametinib (HR OS: 0.55) and vemurafenib plus cobimetinib (HR OS: 0.57).

Our NMA identified the most effective treatment options for advanced melanoma and provided valuable insights into each novel treatment’s relative effectiveness and safety. This information may facilitate evidence-based decision-making and may support the optimisation of treatment and outcomes in everyday clinical practice.

Franken, M.G., Leeneman, B., Gheorghe, M., Uyl-de Groot, C.A., Haanen, J.B.A.G., and van Baal, P.H.M. A systematic literature review and network meta-analysis of effectiveness and safety outcomes in advanced melanoma. 24989. 2019 Eur J Cancer (123):

Concepts Keywords
Bayesian Ipilimumab
Carboplatin Dabrafenib
Cochrane Melanoma
Embase Vemurafenib
Ipilimumab Antineoplastic drugs
Melanoma Bristol-Myers Squibb
Meta Analysis Genentech
Paclitaxel Sulfonamides
Paradigm Cancer treatments
Phase III Clinical medicine
Randomised Controlled Trials Chemical compounds
SLR
Temozolomide
Vemurafenib

Semantics

Type Source Name
drug DRUGBANK Carboplatin
drug DRUGBANK Dabrafenib
drug DRUGBANK Trametinib
drug DRUGBANK Vemurafenib
drug DRUGBANK Cobimetinib
drug DRUGBANK Nivolumab
drug DRUGBANK Ipilimumab
drug DRUGBANK Pembrolizumab
drug DRUGBANK Binimetinib
drug DRUGBANK Encorafenib
drug DRUGBANK Paclitaxel
drug DRUGBANK Temozolomide
drug DRUGBANK Dacarbazine
pathway KEGG Melanoma
disease MESH melanoma

Original Article

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