Dabrafenib and Trametinib vs. Anti-PD(L)1 for the Adjuvant Treatment of Locally Advanced BRAF-Mutant Melanoma: A Systematic Review and Meta-Analysis

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. 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 I2 statistics. This study was registered with PROSPERO (CRD42024553421). Eight observational studies (2,394 patients) met inclusion criteria. No eligible RCTs were identified. Median follow-up ranged from 10-53 months. D + T improved RFS compared to anti-PD(L)1 therapies (HR 0.53, 95%CI 0.40-0.70, p < 0.01; I2=55%). However, no significant difference was observed in overall survival (OS) (HR 0.83, 95%CI 0.60-1.15, p = 0.27; I2=0%). Subgroup and sensitivity analyses yielded similar results. D + T was associated with a higher rate of treatment discontinuation due to adverse events, with a relative risk of 1.57 (95%CI 1.30-1.91, p < 0.01; I2=0%), corresponding to a risk difference of 8% (95%CI 5%-12%, p < 0.01; I2=0%). D + T 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. D + T is superior to anti-PD(L)1 therapies for the adjuvant treatment of BRAF mutant melanoma in terms of RFS. However, no OS difference have been demonstrated, and D + T is associated with a higher risk of treatment discontinuation due to adverse events. These findings highlight the need for individualized treatment decisions based on patient preferences and tolerability.