Cost-effectiveness of dabrafenib and trametinib in combination as adjuvant treatment of BRAF V600E/K mutation-positive melanoma from a US healthcare payer perspective

Abstract

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.

Cost-Benefit Implication of Gene Expression Profiling and Adjuvant Therapy in Stage IIIA Melanoma

“…Cost of 31-GEP was based on the Medicare Clinical Laboratory Fee Schedule. Drug and drug administration costs for pembrolizumab, dabrafenib/trametinib, and ipilimumab were recently published (8,9,18). Radiographic surveillance in the setting of stage IIIA disease, and in the setting of distant metastases, was derived from National Comprehensive Cancer Network recommendations for stage IIB-IV disease (6).…”

Economic evaluation of adverse events of dabrafenib plus trametinib versus nivolumab in patients with advanced BRAF-mutant cutaneous melanoma for adjuvant therapy in Germany

“…A rather neglected question in the published health economic literature is the role of the adverse event profiles of both therapies, their comparisons, and their economic consequences [44].…”

“…A rather neglected question in the published health economic literature is the role of the adverse event profiles of both therapies, their comparisons, and their economic consequences [ 44 ]. Here, we attempt to analyze the economic impact of the side effects in both therapies, based on the published results of both trials.…”

Elucidating value: the role of cost-effectiveness analysis in the decision-making process for the management of BRAF V600E/K mutation-positive melanoma

“…In a study published in the Journal of Medical Economics, Gerbasi et al fathom the cost-effectiveness profile of dabrafenib with trametinib as an adjuvant treatment of melanoma 7 . They constructed a non-homogenous semi-Markov cohort model which consists of five discrete health states: (1) Relapse-free survival (RFS) state; (2) post locoregional recurrence (LR) state; (3) post distant recurrence (DR) first-line treatment (1 L DR) state; (4) post DR second-line treatment (2 L DR) state; and (5) dead state.…”