Cost-effectiveness of treatment strategies for BRAF-mutated metastatic melanoma

Abstract

Purpose: Genetically-targeted therapies are both promising and costly advances in the field of oncology. Several treatments for metastatic melanoma with a mutation in the BRAF gene have been approved. They extend life but are more expensive than the previous standard of care (dacarbazine). Vemurafenib, the first drug in this class, costs $13,000 per month ($207,000 for a patient with median survival). Patients failing vemurafenib are often given ipilimumab, an immunomodulator, at $150,000 per course. Assessment of cost-effectiveness is a valuable tool to help navigate the transition toward targeted cancer therapy.

Methods: We performed a cost-utility analysis to compare three strategies for patients with BRAF+ metastatic melanoma using a deterministic expected-value decision tree model to calculate the present value of lifetime costs and quality-adjusted life years (QALYs) for each strategy. We performed sensitivity analyses on all variables.

Results: In the base case, the incremental cost-effectiveness ratio (ICER) for vemurafenib compared with dacarbazine was $353,993 per QALY gained (0.42 QALYs added, $156,831 added). The ICER for vemurafenib followed by ipilimumab compared with vemurafenib alone was $158,139. In sensitivity analysis, treatment cost had the largest influence on results: the ICER for vemurafenib versus dacarbazine dropped to $100,000 per QALY gained with a treatment cost of $3600 per month.

Conclusion: The cost per QALY gained for treatment of BRAF+ metastatic melanoma with vemurafenib alone or in combination exceeds widely-cited thresholds for cost-effectiveness. These strategies may become cost-effective with lower drug prices or confirmation of a durable response without continued treatment.

Figure 1. Decision Tree Model: The decision tree model used to estimate outcomes for the first year following treatment initiation.

The decision nodes list the strategies modeled and the chance nodes list the probabilities of different clinical events during the first year. The path probability is the chance a patient will follow each specific path. The QALY and cost numbers in the “for terminal nodes” column is the average values over the course of a year for each patient taking that path, and the “intermediate product” column shows those individual averages adjusted for the proportion of people taking that path. Beneath these columns is the summation of the columns, representing to average costs and QALYs associated with the strategy. Beneath these averages in the second and third strategies are the differences and ICERs comparing each strategy to the strategy directly above it.

Figure 2. Decision Tree Model for Second-Line Ipilimumab: See format and conventions described in Figure 1 .