Background: Previous results of the COMBI-AD trial (NCT01682083) showed a significant relapse-free survival (RFS) benefit with 12 mo of adjuvant D+T vs placebo (PBO) in pts with high-risk resected stage III BRAF V600E/K–mutant melanoma. In the primary analysis, 3-year RFS rates with D+T vs PBO were 58% vs 39% (hazard ratio [HR], 0.47 [95% CI, 0.39-0.58]; P< .001). An interim analysis of overall survival (OS) yielded 3-year OS rates of 86% with D+T vs 77% with PBO (HR, 0.57 [95% CI, 0.42-0.79]). Here we report data from 5-year analyses including long-term RFS and an updated cure rate model. Methods: COMBI-AD is a randomized, Phase III trial evaluating 12 mo of adjuvant D 150 mg twice daily + T 2 mg once daily vs 2 matched PBOs in pts with resected stage III BRAF V600E/K–mutant melanoma. Pts were stratified by BRAF status and disease stage (per AJCC 7 criteria). The primary endpoint is RFS; secondary endpoints include OS and distant metastasis–free survival (DMFS). A Weibull mixture cure rate model was applied to estimate the fraction of pts who will remain relapse free in the long term. As all patients had completed treatment by the time of the primary analysis, updated safety analyses were not performed. Results: This analysis represents a median follow-up of 60 mo for the D+T arm and 59 mo for the PBO arm. As of the data cutoff (Nov 8, 2019), 190 of 438 pts in the D+T arm and 262 of 432 pts in the PBO arm had an RFS event. Median RFS was not reached (NR; 95% CI, 47.9 mo-NR) with D+T vs 16.6 mo (95% CI, 12.7-22.1 mo) with PBO (HR, 0.51 [95% CI, 0.42-0.61]). The 4- and 5-year RFS rates were 55% (95% CI, 50%-60%) and 52% (95% CI, 48%-58%) with D+T vs 38% (95% CI, 34%-43%) and 36% (95% CI, 32%-41%) with PBO. These findings match those estimated by the cure rate model. The RFS benefit with D+T was evident across all AJCC 7 substages (HR [95% CI]: IIIA, 0.61 [0.35-1.07]; IIIB, 0.50 [0.37-0.67]; IIIC, 0.48 [0.36-0.64]). Median DMFS was NR in either arm but favored D+T (HR, 0.55 [95% CI, 0.44-0.70]). OS was not updated at this data cutoff as the prespecified number of events for the final OS analysis had not yet occurred. Conclusions: This 5-year analysis confirms the long-term benefit of adjuvant D+T in pts with resected stage III BRAF V600E/K–mutant melanoma. Clinical trial information: NCT01682083