Network meta-analysis of therapies for previously untreated advanced BRAF-mutated melanoma.

The spectrum of treatment options for patients with metastatic BRAF-mutated melanoma is broad, spanning multiple treatment classes. However, there is a lack of head-to-head evidence comparing targeted and immunotherapies. The purpose of this study is to conduct a network meta-analysis (NMA) in previously untreated, BRAF-mutated melanoma patients and estimate the relative efficacy of systemic therapies for this patient population at the treatment level. The literature review included searches of MEDLINE, EMBASE, and the Cochrane Central Registry of Controlled Trials (CENTRAL) to November 2018. Randomized controlled trials of previously untreated patients with advanced melanoma were eligible if at least one intervention was either a targeted or immune therapy. Relative treatment effects were estimated by fixed effect Bayesian NMAs on progression-free survival (PFS) and overall survival (OS), based on the hazard ratio. Combination dabrafenib with trametinib (HR 0.22 [95% CrI 0.17, 0.28] vs dacarbazine) and combination vemurafenib with cobimetinib (HR 0.22 [95% CrI 0.17, 0.29] vs dacarbazine) were likely to rank as the most favorable treatment options for PFS, while combination nivolumab with ipilimumab was likely to be the most efficacious in terms of OS (HR 0.33 [0.24, 0.47] vs dacarbazine). The findings highlight the efficacy of combination PD-1 with CTLA-4 inhibitors and combination BRAF with MEK inhibitors in the treatment of advanced melanoma. However, as few trials informed each treatment comparison, research is needed to further refine our understanding of this complex and rapidly evolving treatment landscape.

Zoratti MJ ，Devji T ，Levine O ，Thabane L ，Xie F ... -  《-》

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

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 MG ，Leeneman B ，Gheorghe M ，Uyl-de Groot CA ，Haanen JBAG ，van Baal PHM ... -  《-》

Indirect treatment comparison of dabrafenib plus trametinib versus vemurafenib plus cobimetinib in previously untreated metastatic melanoma patients.

Daud A ，Gill J ，Kamra S ，Chen L ，Ahuja A ... -  《Journal of Hematology & Oncology》

Comparative efficacy of combination immunotherapy and targeted therapy in the treatment of BRAF-mutant advanced melanoma: a matching-adjusted indirect comparison.

Atkins MB ，Tarhini A ，Rael M ，Gupte-Singh K ，O'Brien E ，Ritchings C ，Rao S ，McDermott DF ... -  《-》

Modeled Prognostic Subgroups for Survival and Treatment Outcomes in BRAF V600-Mutated Metastatic Melanoma: Pooled Analysis of 4 Randomized Clinical Trials.

Hauschild A ，Larkin J ，Ribas A ，Dréno B ，Flaherty KT ，Ascierto PA ，Lewis KD ，McKenna E ，Zhu Q ，Mun Y ，McArthur GA ... -  《-》