Objective: The COMBI-AD trial demonstrated the efficacy and safety of dabrafenib and trametinib in combination vs placebo as adjuvant treatment of patients with BRAF V600E/K mutation-positive resected Stage IIIA (lymph node metastasis >1 mm), IIIB, or IIIC melanoma. This analysis evaluated the cost-effectiveness of dabrafenib and trametinib vs observation from a US healthcare payer perspective. Methods: This evaluation employed a non-homogeneous, semi-Markov, cohort model with health states for relapse-free survival (RFS), post-locoregional recurrence (LR), post-distant recurrence (DR) receiving first-line treatment, and post-DR receiving second-line treatment. A 50-year modeling time horizon was used. Transition probabilities were estimated based on individual patient data (IPD) from the COMBI-AD trial. Health-state utilities were estimated using EuroQol (EQ-5D) index values from COMBI-AD and published sources. Direct medical costs associated with treatment of melanoma were considered, including costs of BRAF mutation testing, medication and administration costs for adjuvant and metastatic treatments, costs of treating recurrence, and costs of adverse events. Costs and qualityadjusted life-years (QALYs) were discounted at 3.0% annually. Results: Compared with observation, adjuvant dabrafenib and trametinib was estimated to result in a gain of 2.15 QALYs at an incremental cost of $74,518. The incremental cost-effectiveness ratio (ICER) was estimated to be $34,689 per QALY. In deterministic sensitivity analyses, the ICER was sensitive to the cost of dabrafenib and trametinib and the distribution used for projecting RFS beyond the end of follow-up in the COMBI-AD trial. At a cost-effectiveness threshold of $100,000 per QALY, the probability that dabrafenib and trametinib is cost-effective was estimated to be 92%. Conclusions: Given generally-accepted cost-effectiveness threshold values in the US, dabrafenib plus trametinib is likely to be a cost-effective adjuvant therapy for patients with BRAF mutation positive melanoma. These results may be useful for policy-makers in their deliberations regarding reimbursement and access to this treatment.

Background Past research suggests that patients with early- and late-stage melanoma will endure adverse events and inconvenient treatment regimens for improved survival. Evidence about the preferences of Canadian patients and physicians for novel adjuvant treatments for melanoma is unavailable.Methods Patient and physician preferences for adjuvant treatments for melanoma were assessed in an online discrete choice experiment (dce). Treatment alternatives were characterized by 8 attributes with respect to dosing regimen, efficacy, and toxicities, with levels corresponding to those for dabrafenib–trametinib, nivolumab, pembrolizumab, and interferon. For patients, the effects of melanoma on quality of life and ability to work and perform activities of daily living were also assessed. Patients were recruited by Canadian melanoma patient advocacy groups through e-mail and social media. Physicians were recruited by e-mail.Results Of 94 patients who started the survey, 51 completed 1 or more dce questions. Of 166 physicians sent the e-mail invitation, 18 completed 1 or more dce questions. For patients, an increased probability of remaining cancer-free over 21 months was the most important attribute. For physicians, an increased chance of the patient’s remaining alive over 36 months was the most important attribute. Patients and physicians chose active treatment over no treatment 85% and 86% of the time respectively and a treatment with attributes consistent with dabrafenib–trametinib 71% and 67% of the time respectively. A substantial proportion of patients reported worrying about future diagnostic tests and their cancer coming back.Conclusions Canadian patients and physicians are generally concordant in their preferences for adjuvant melanoma treatments, preferring active treatment to no treatment and dabrafenib–trametinib to other options.

BACKGROUND: Before the approval of dabrafenib and trametinib in combination, there were no approved therapies in the adjuvant setting that target the RAS/RAF/MEK/ERK pathway. OBJECTIVE: To evaluate the budget impact of dabrafenib and trametinib in combination for adjuvant treatment of patients with BRAF V600 mutationpositive resected Stage IIIA, IIIB, or IIIC melanoma from a U.S. commercial payer perspective using data from the COMBI-AD trial, as well as other sources.

Objectives: 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. Methods: 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. Results: 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 longterm RFS. Conclusions: 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.

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