Tampa, FL—Combining dabrafenib (Tafinlar) with trametinib (Mekinist) as upfront treatment for patients diagnosed with BRAF V600 mutation–positive metastatic melanoma should lead to improved survival, but it increases the direct costs of treatment compared with other first-line therapies. Dabrafenib plus trametinib may be a cost-effective option from a payer perspective, depending on the threshold value used to determine cost-effectiveness. These were the findings of a study presented at the 2014 Academy of Managed Care Pharmacy meeting.
The study assessed the cost-effectiveness of the combination of dabrafenib plus trametinib compared with other common therapies (dabrafenib, trametinib, vemurafenib [Zelboraf], dacarbazine [DTIC], but not ipilimumab [Yervoy] or interleukin-2) for the first-line treatment of BRAF V600/E/K mutation–positive unresectable or metastatic melanoma.
The direct medical costs associated with the treatment of metastatic melanoma over a 30-year period were considered from treatment initiation to approximate a lifetime projection. The future costs, life-years, and quality-adjusted life-years (QALYs) were discounted at 3% annually.
The estimates of projected median progression-free survival were approximately twice as long for the dabrafenib-trametinib combination compared with the comparators: 10.36 months for dabrafenib-trametinib versus 5.98 months, 5.52 months, 5.98 months, and 3.91 months for dabrafenib, trametinib, vemurafenib, and DTIC, respectively.
The overall survival was projected to be from 7 months to approximately 15 months longer with the combination—25.55 months for dabrafenib plus trametinib versus 15.19 months, 18.18 months, 15.19 months, and 9.67 months for dabrafenib, trametinib, vemurafenib, and DTIC, respectively.
The threshold value for cost-effectiveness may be as high as $200,000 per QALY, according to a 2003 study by Ubel and colleagues; this estimate was based on a review of several frequently used clinical examples with cost-effectiveness ratios that exceeded conventional limits.
The expected costs were higher for the combination of dabrafenib plus trametinib than for comparators in more than 99% of simulations. QALYs are higher for dabrafenib plus trametinib in 75.9% of the simulations versus trametinib and in 97.1% of the simulations versus DTIC. The combination of dabrafenib plus trametinib is projected to have higher costs and lower QALYs in 2.9% of the simulations versus DTIC to 22.9% of the simulations versus trametinib.
Using a threshold for cost-effectiveness of $200,000 per QALY gained, the probability that the combination of dabrafenib plus trametinib and its comparators are cost-effective is 41% for dabrafenib plus trametinib, 20.6% for dabrafenib, 36.1% for trametinib, 0% for vemurafenib, and 2.3% for DTIC.
The dabrafenib-trametinib combination is more likely to be preferred compared with the other therapies if the threshold value for cost-effectiveness is approximately $180,000 per QALY or greater, according to the researchers.
The investigators stated that the cost-effectiveness of the dabrafenib-trametinib combination should continue to be evaluated as survival data continue to mature and as data from large phase 3 studies become available.
