OBJECTIVES : The treatment landscape of adjuvant melanoma is evolving with the introduction of targeted therapy (i.e. dabrafenib plus trametinib) and immune checkpoint inhibitors such as pembrolizumab and nivolumab. The objective was to compare efficacy of dabrafenib plus trametinib against other approved adjuvant therapies for melanoma via network meta-analysis (NMA) based on an SLR update.

METHODS : The SLR was updated in September 2020 via a search of key biomedical databases and conferences. The SLR update included Phase II/III randomized controlled trials (RCTs) assessing dabrafenib plus trametinib, nivolumab, pembrolizumab, ipilimumab, vemurafenib, chemotherapy and interferons (IFNs) in treatment of adult patients (≥18 years) in the adjuvant melanoma setting. The outcomes of interest were relapse-free survival (RFS), overall survival (OS), and distant metastasis-free survival (DMFS). Bayesian network meta-analysis was applied for the pairwise comparisons among treatments.

RESULTS : The SLR update identified 37 RCTs assessing targeted therapies, immune-checkpoint inhibitors, chemotherapy, and IFNs. The SLR update identified long-term data for key trials i.e. COMBI-AD trial (dabrafenib plus trametinib), CheckMate-238 trial (nivolumab) and Keynote-054 trial (pembrolizumab). The NMA results showed that that dabrafenib plus trametinib had lower estimated hazards of respective events for all efficacy parameters relative to all other treatments. For RFS, differences were statistically significant in favour of dabrafenib plus trametinib compared to ipilimumab (HR: 0.68 [95% CI: 0.53, 0.87), chemotherapy (HR: 0.62 [95% CI: 0.47, 0.82), placebo (HR: 0.51 [95% CI: 0.42, 0.61), and different regimens of IFN-α. The results were found to be comparable for RFS between dabrafenib plus trametinib and immune-checkpoint inhibitors i.e. nivolumab (HR: 0.95 [95% CI: 0.70, 1.29) and pembrolizumab (HR: 0.86 [95% CI: 0.67, 1.12).

CONCLUSIONS : The NMA findings showed that dabrafenib plus trametinib has improved efficacy over treatment options such as ipilimumab, interferons and chemotherapy and comparable efficacy with immune-checkpoint inhibitors in the adjuvant setting.