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

Background: 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.

Methods: 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).

Results: 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%).

Conclusions: 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.

Implications For Practice: 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.