First-line pembrolizumab every 3 weeks followed by second-line ipilimumab, and first-line nivolumab followed by second-line ipilimumab are cost-effective strategies in patients with advanced melanoma expressing wild-type BRAF.
First-line pembrolizumab every 3 weeks followed by second-line ipilimumab, and first-line nivolumab followed by second-line ipilimumab are cost-effective strategies in patients with advanced melanoma expressing wild-type BRAF. These were the findings of a study published in the Journal of Clinical Oncology.
Patients with advanced disease have a much poorer prognosis, with only a 17% 5-year survival rate. However, patients with a more localized disease witness a 98% 5-year survival rate. Multiple phase 3 clinical trials that have evaluated nivolumab, ipilimumab, and pembrolizumab have found that while outcomes improve, these treatments are associated with adverse events and are quite expensive—the average annual cost of treatment with each drug easily surpasses $100,000. This makes it much harder to make decisions on the sequence of treatments and the dosing schedule.
For their current analysis, the authors developed a Markov model to estimate lifetime costs and quality-adjusted life years (QALY) for treatment sequences with first-line nivolumab, ipilimumab, nivolumab plus ipilimumab, pembrolizumab every 2 weeks, and pembrolizumab every 3 weeks. Patient health states were defined for initial treatment, first and second progression, and death. Rates for drug discontinuation, frequency of adverse events, disease progression, and death, obtained from randomized phase 3 trials, were used to determine the likelihood of transition between states.
The model showed that pembrolizumab every 3 weeks followed by second-line ipilimumab was more effective and less costly than the standard-of-care dacarbazine. The second cost-effective treatment was first-line nivolumab followed by second-line ipilimumab or ipilimumab followed by nivolumab. The incremental cost-effectiveness ratio of nivolumab followed by ipilimumab was $90,871/QALY. First-line nivolumab plus ipilimumab, followed by carboplatin plus paclitaxel chemotherapy, produced an incremental cost effectiveness ratio of $198,867/QALY.
The authors wrote that the drug acquisition cost of first-line ipilimumab and the cost of managing immune-related adverse events were significant factors that influenced their model.
Kohn CG, Zeichner SB, Chen Q, Montero AJ, Goldstein DA, Flowers CR.
Cost-effectiveness of immune checkpoint inhibition in BRAF wild-type advanced melanoma [published online February 21, 2017]. J Clin Oncol. doi: 10.1200/JCO.2016.69.6336.