Cost-effectiveness of pembrolizumab for the adjuvant treatment of resected high-risk stage III melanoma in the United States

Abstract

Aims: To evaluate the cost-effectiveness of adjuvant pembrolizumab relative to observation alone following complete resection of high-risk stage III melanoma with lymph node involvement, from a US health system perspective. Materials and methods: A Markov cohort model with four health states (recurrence-free, locoregional recurrence, distant metastases, and death) was developed to estimate costs, life-years, and qualityadjusted life-years (QALYs) associated with pembrolizumab vs observation over a lifetime (46-year) horizon. Using a parametric multi-state modeling approach, transition probabilities starting from recurrence-free were estimated based on patient-level data from KEYNOTE-054 (NCT02362594), a direct head-to-head phase 3 trial. Post-recurrence transition probabilities were informed by real-world retrospective data and clinical trials in advanced melanoma. Health state utilities and adverse eventrelated disutility were derived from KEYNOTE-054 trial data and published literature. Costs of drug acquisition and administration, adverse events, disease management, and terminal care were estimated in 2018 US dollars. Deterministic and probabilistic sensitivity analyses were conducted to assess robustness. Results: Over a lifetime horizon, adjuvant pembrolizumab and observation were associated with total QALYs of 9.24 and 5.95, total life-years of 10.54 and 7.15, and total costs of $489,820 and $440,431, respectively. The resulting incremental cost-effectiveness ratios (ICERs) for pembrolizumab vs observation were $15,009/QALY and $14,550/life-year. Across the range of input values and assumptions tested in deterministic sensitivity analyses, pembrolizumab ranged from being a dominant strategy to having an ICER of $57,449/QALY vs observation. The ICER was below a willingness-to-pay threshold of $100,000/QALY in 90.2% of probabilistic simulations. Limitations: Long-term extrapolation of outcomes was based on interim results from KEYNOTE-054, with a median follow-up of 15 months. Conclusions: Based on common willingness-to-pay benchmarks, pembrolizumab is highly cost-effective compared with observation alone for the adjuvant treatment of completely resected stage III melanoma in the US. ARTICLE HISTORY

Cost-Effectiveness of Pembrolizumab for the Adjuvant Treatment of Melanoma Patients with Lymph Node Involvement Who Have Undergone Complete Resection in Argentina

“…These results are in accordance with those seen in the US setting, where adjuvant pembrolizumab was found to be highly cost-effective versus watchful waiting (15,009 USD/QALY gained) for patients with high-risk stage III melanoma [ 46 ]. The slightly lower number of life-years gained with adjuvant pembrolizumab in Argentina (2.94) versus the US (3.39) reflects higher mortality rates in the Argentinian population as compared with those seen in North America, and different distribution of subsequent advanced melanoma treatments in each country.…”

An Economic Evaluation of Pembrolizumab Versus Other Adjuvant Treatment Strategies for Resected High-Risk Stage III Melanoma in the USA

“…With the recent FDA approval of several adjuvant treatments for resected stage III melanoma, comprehensive economic evaluations of these treatments are needed to inform reimbursement decision-making by payers. The cost-effectiveness of pembrolizumab was previously evaluated relative to routine observation in a US-based study [26]. Prior submissions to NICE have assessed the costeffectiveness of pembrolizumab [27], nivolumab [71], and dabrafenib + trametinib [72] from a UK national payer perspective, each focusing on the comparison with observation.…”

“…A Markov cohort structure was developed in accordance with methods guidance for state transition models [25]. The structure was previously applied in a submission to the National Institute for Health and Care Excellence (NICE) and in a published US-based economic evaluation focusing on the comparison of pembrolizumab versus observation [26,27]. In this new application, the model framework was expanded to evaluate a broader set of adjuvant comparators.…”

Cost–Utility Analysis of Nivolumab in Adjuvant Treatment of Melanoma in France

“…The ICUR of nivolumab versus low-dose interferon (the therapeutic strategy closest on the efficiency frontier) was €37,886/QALY. Analyses conducted in other countries achieved lower ICUR levels that may be primarily explained by their pairwise approach versus observation [ 35 – 37 ].…”

“…Whether it was adapted for earlier stages, such as for the adjuvant treatment of surgically resected tumours could be subject to discussion. Indeed, another study recently published for the adjuvant treatment of melanoma [ 35 ] used a Markov state transition model. The choice between both modelling approaches was further reviewed by Smare et al.…”