What is the evidenceSee evidence matrix in Epistemonikos later
We identified five systematic reviews [3,9–12] including seven primary studies [4–8,13,14] reported in seventeen references [4–8,13–24] that included one of the interventions of interest. All the studies were randomized trials.We did not find studies directly comparing dabrafenib plus trametinib versus nivolumab. Therefore, this analysis included network meta-analyses with indirect comparisons.Three systematic reviews [3,10,11] were bayesian network meta-analyses, and two [9,12] were frequentist network meta-analysis.the median follow-up for the trials including the interventions of interest in the network meta-analysis fluctuates between 5.3 and 46.9 months.
What types of patients were included*
All the studies included adults with advanced cutaneous melanoma (unresectable stage III and metastatic stage IV).Five studies [4,6,7,13,14] included patients with no previous treatment. One study [8] included patients who progressed to one previous treatment, and one study [5] included patients with no line of treatment restriction.Four studies [4,5,13,14] included only patients with BRAF mutation. Two studies [6,8] included patients independently of BRAF mutation status, and one [7] included only patients with BRAF wild-type.
What types of interventions were included*
Two studies [4,5] compared dabrafenib plus trametinib versus dabrafenib alone, one study [13] against vemurafenib, and one study against pembrolizumab plus dabrafenib plus trametinib [14].One study [7] compared nivolumab against dacarbazine, and another study against chemotherapy (dacarbazine plus carboplatin or paclitaxel plus carboplatin) [8]. The last study [6] was a three-arm study and compared nivolumab plus ipilimumab versus, either nivolumab or ipilimumab alone.All studies are part of four network meta-analyses, that indirectly compared the treatments under analysis.
What types of outcomes were measured
The studies reported multiples outcomes, which were aggregated into a systematic review and defined as follows:
Overall survival was defined as the risk of dying from any given cause.
Progression-free survival as the risk of progression using one of the interventions.
Response to the treatment as the probability of having a complete response or partial response to the treatment with one intervention.
Toxicity as the risk of presenting a severe or grade III/IV, adverse event during the treatment with one of the interventions.
Health-related quality of life as a subjective and multidimensional concept that accounts for how an individual perceives their health.
*The information about primary studies is not extracted directly from primary studies but from identified systematic reviews unless otherwise stated.
