Economic Evaluation of Systemic Treatments for Advanced Melanoma: A Systematic Review

Abstract

Background: Many high cost treatments for advanced melanoma have become available in recent years. National health technology assessment agencies have raised concerns regarding uncertainty in their clinical and cost-effectiveness. Objective: The aim of this systematic review is to identify economic evaluations of treatments for advanced melanoma and review model assumptions, outcomes, and quality as preparation for a health technology assessment. Methods: A search of Embase, MEDLINE, EconLit, and the Cochrane Database was conducted. Only studies using decisionanalytic models were included. Two authors independently completed full-text review and data extraction. Results: Fifteen studies were identified. There were major differences in the structural assumptions underpinning the models. There was general agreement in study conclusions, although the predicted costs and quality-adjusted life years for each treatment varied. BRAF monotherapy (vemurafenib, dabrafenib) or BRAF/MEK combination therapy (BRAF monotherapy with cobimetinib or trametinib) has not been shown to be cost-effective in any jurisdiction. PD-1 inhibitors (pembrolizumab, nivolumab) are consistently found to be cost-effective compared with ipilimumab, although their costeffectiveness compared with chemotherapy is not established. Combination therapy with nivolumab and ipilimumab is unlikely to be cost-effective in any setting. One study including all agents found that none of the new treatments were cost-effective relative to chemotherapy. Publication of the study in a health economics journal is associated with better reporting of and higher-quality assessment than those published in clinical journals. Conclusion: Despite differences in model structures and assumptions, the conclusions of most included studies were consistent. Health technology assessment has a key role in maximizing value from high-cost innovative treatments. Consideration should be given to divestment from BRAF/MEK inhibitors and ipilimumab in favor of reimbursement of PD-1 inhibitors.

Transferability of Economic Evaluations of Treatments for Advanced Melanoma

“…The systematic review identified 660 records, and 131 underwent full-text review [21]. Fifteen academic studies, published between 2000 and 2018, were eligible for inclusion (Appendix 1, Table A2, see ESM) [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49].…”

“…Assessment of transferability was difficult due to poor quality reporting [21]. Unsurprisingly, none of the identified CEAs demonstrated complete generic transferability to the Irish setting as none were aligned with the national reference case for CEA.…”

“…CEAs were identified through systematic review [21]. De novo decision analytic models investigating the cost effectiveness of treatments for advanced melanoma were eligible for inclusion, regardless of line of treatment.…”

“…All studies with an outcome of cost per QALY, cost per life-year gained (LYG) or alternative measure of health outcome were included. The search was conducted in the Cochrane database, MEDLINE, Embase and EconLit in September 2018 [Appendix Table A1, see electronic supplementary material (ESM)] [21]. Data on model parameters, predicted total costs, incremental QALYs, incremental costs, ICERs, cost-effectiveness threshold and study conclusions were extracted by two authors independently (CG, LMcC).…”

Gas Plasma-Oxidized Liquids for Cancer Treatment: Preclinical Relevance, Immuno-Oncology, and Clinical Obstacles

“…To enhance the transferability of pre-clinical animal models, gas plasma-oxidized liquids should, therefore, be compared to or combined with standard cytostatics. However, across all in vivo experiments, only two studies combined gas plasma-oxidized liquids with drugs [63,67], with both studies using compounds not being standard drugs for systemic melanoma treatment [124]. This is not necessarily a weakness of these studies, because through their combination with the oxidizing solutions, old or new substances can move into the focus of research (if an additive effect is observed).…”