PCN87 COST-EFFECTIVNESS ANALYSIS OF DABRAFENIB PLUS TRAMETINIB AS ADJUVANT TREATMENT FOR BRAF V600 MUTATION-POSITIVE MELANOMA AFTER SURGICAL RESECTION IN CANADA- A SOCIETAL PERSPECTIVE

Abstract

The COMBI-AD trial demonstrated the efficacy and safety of dabrafenib plus trametinib (D+T) vs. placebo as adjuvant treatment of patients with BRAF V600 mutation-positive, high risk resected Stage III melanoma. This analysis evaluated the cost-effectiveness of dabrafenib and trametinib in this indication from a Canadian societal perspective. The cost-effectiveness of D+T versus observation (OBS, represented by placebo arm of COMBI-AD) was estimated using a non-homogeneous, semi-Markov cohort model with states for relapse-free survival (RFS), post-locoregional recurrence, post-distant recurrence (DR) receiving first-line treatment, and post-DR receiving second-line treatment. The incremental cost effectiveness ratio (ICER) was defined as the incremental cost per quality-adjusted life-year (QALY) gained. A 35-year time horizon was used. Transition probabilities for each six-month model cycle were estimated using data from COMBI-AD. Health-state utilities were estimated using EQ-5D index values collected in COMBI-AD and published sources. Direct costs of melanoma treatment (BRAF mutation testing, medication and administration costs for adjuvant and metastatic treatments, treatment of recurrence, and adverse events) and indirect costs of productivity losses were considered. Costs ($ CAN) and QALYs were discounted at 1.5% annually. In the base case D+T was estimated to result in a gain of 2.60 QALYs vs. OBS, at an incremental cost of $75,085. The ICER of D+T vs. OBS was $28,865 per QALY gained based on deterministic analyses and $29,520 based on the mean of probabilistic analyses. Results are sensitive to parametric distributions used for projecting long-term RFS. For patients with BRAF V600 mutation-positive, high-risk Stage III melanoma who have been surgically resected, D+T is projected to result in substantial gains in QALYs compared with OBS. At the current list price in Quebec, D+T is cost-effective vs OBS based on commonly-referenced threshold values. These results may be useful in deliberations regarding reimbursement and access to this treatment in Canada.