Dabrafenib and trametinib vs anti-PD(L)1 for the adjuvant treatment of locally advanced BRAF-mutant melanoma: a systematic review and meta-analysis.

Abstract

<h4>Background</h4>Both dabrafenib and trametinib (D + T) and anti-PD(L)1s have been shown to improve recurrence-free survival (RFS) in patients with stage III or resected stage IV BRAF-mutant melanoma. However, no randomized controlled trials (RCTs) have directly compared them in the adjuvant setting, creating uncertainties about the optimal approach. This systematic review and meta-analysis address this knowledge gap.<h4>Methods</h4>A comprehensive search of PubMed, Embase, and Scopus was conducted to identify studies comparing D + T with anti-PD(L)1 therapies. Studies with overlapping populations were excluded. Statistical analyses employed a random-effects model, with heterogeneity assessed via I 2 statistics. This study was registered with PROSPERO (CRD42024553421).<h4>Results</h4>Eight observational studies (2394 patients) met the inclusion criteria. No eligible RCTs were identified. Median follow-up ranged from 10 to 53 months. Dabrafenib and trametinib improved RFS compared to anti-PD(L)1 therapies (hazard ratio [HR] 0.53, 95% CI, 0.40-0.70, P < .01; I 2 = 55%). However, no significant difference was observed in overall survival (OS) (HR 0.83, 95% CI, 0.60-1.15, P = .27; I 2 = 0%). Subgroup and sensitivity analyses yielded similar results. Dabrafenib and trametinib was associated with a higher rate of treatment discontinuation due to adverse events (AEs), with a relative risk of 1.57 (95% CI, 1.30-1.91, P < .01; I 2 = 0%), corresponding to a risk difference of 8% (95% CI, 5%-12%, P < .01; I 2 = 0%).<h4>Conclusions</h4>Dabrafenib and trametinib demonstrated superiority over anti-PD(L)1 therapies in terms of RFS. However, no OS benefit was observed, and D + T was associated with a higher risk of treatment discontinuation. These findings should be considered when counseling patients, as the choice of adjuvant therapy may need to be tailored to individual preferences and tolerability.