OBJECTIVES: A cost-effectiveness model was developed to estimate the ICER of dabrafenib+trametinib (D+T) compared to watchful waiting (WW) in BRAF+ adjuvant melanoma, from a French healthcare perspective. Methods were based on HAS guidelines and international good research practices for modelling.

METHODS: A non-homogeneous semi-Markov cohort model was used with states defined on recurrence and death, including: Relapse-free survival (RFS), locoregional recurrence, distant recurrence (1^st line and 2^nd line) and death. A lifetime horizon was used, from treatment initiation. Marginal parametric distributions were fitted on individual data from the COMBI-AD trial to extrapolate time spent in each health state. Distributions were distinguished between therapeutic classes for 1^st line distant melanoma. Overall survival was corrected with general population mortality for locoregional melanoma and long-term survivors with distant melanoma. Health-state utilities were estimated using EQ-5D data from COMBI-AD. Resource utilization and costs included drug acquisition and administration, routine surveillance and management of adverse events, melanoma recurrences and end-of-life.

RESULTS: In the COMBI-AD trial and after extrapolation, D+T showed significant advantage in reducing the risk of recurrence vs. WW (respectively 47% and 56% of patients developed a distant melanoma over lifetime). D+T was associated with lower costs (Δ=-20,140€) and higher QALYs (Δ=+1.68) than WW. Deterministic and probabilistic sensitivity analyses showed consistency with base case findings. Results were mainly sensitive to variations in extrapolation of the RFS and therapeutic patterns defined for each arm in metastatic setting.

CONCLUSIONS: D+T represents a clinically significant advancement for adjuvant treatment of resected BRAF V600 mutation-positive high-risk stage III melanoma. D+T dominates WW with gains in QALYs and a lower cost. New melanoma adjuvant treatments including immune checkpoint inhibitors have shown great results vs. WW by delaying recurrences and increasing the proportion of patients cured. The relative positioning of these new strategies still needs to be defined.