Cost-effectiveness and budget impact analysis of pembrolizumab as an adjuvant treatment of resected stage III melanoma from an Australian healthcare system perspective.

IMPORTANCE: Stage III melanoma carries a substantial risk of recurrence despite complete surgical resection. Pembrolizumab improves recurrence-free survival, but its cost-effectiveness and potential budget impact in Australia remain important considerations. This study aims to evaluate the cost-effectiveness and potential budget impact of adjuvant pembrolizumab vs standard care (chemotherapy) for resected stage III melanoma from the Australian health care system perspective and to estimate the potential 5-year budget impact under alternative eligible population and uptake scenarios.

METHODS: A lifetime state-transition Markov model was developed for patients with completely resected stage III melanoma. Health states included recurrence-free, locoregional recurrence, distant metastasis, and death. Transition probabilities were derived from published trials and long-term follow-up data, with mortality informed by Australian life tables. Australian cost inputs were derived from the Pharmaceutical Benefits Scheme and Medicare Benefits Schedule, and health state utilities were obtained from published literature. Costs and QALYs were discounted at 5% annually. Outcomes included lifetime costs, QALYs, ICERs, INMBs, and cost-effectiveness probabilities. Cost-effectiveness was interpreted using AU$50,000 per QALY gained as the primary Australian willingness-to-pay (WTP) reference value; AU$100,000 per QALY was considered only as a scenario analysis and was not used for the main conclusion. Parameter uncertainty was assessed using deterministic and probabilistic sensitivity analyses. A scenario-based budget impact analysis was also conducted over a 5-year horizon using alternative eligible population assumptions and conservative, moderate, and high uptake scenarios.

RESULTS: Pembrolizumab increased both lifetime costs and QALYs compared with standard care, with a base-case ICER of AU$43,132 per QALY gained. At the primary Australian reference value of AU$50,000 per QALY gained, pembrolizumab had a positive INMB of AU$15,247 and a 65.3% probability of being cost-effective. Results were most sensitive to the recurrence-free survival hazard ratio, pembrolizumab cost, and utility estimates for recurrence states. Using the modelled lifetime incremental cost, the 5-year budget impact ranged from AU$61.30 million under the conservative population and conservative uptake scenario to AU$581.70 million under the upper-bound population and high uptake scenario. Using the treatment-period incremental cost, the corresponding range was AU$88.87 million to AU$843.33 million.

CONCLUSION: Adjuvant pembrolizumab was likely to be cost-effective for appropriately selected patients with resected stage III melanoma in Australia when interpreted against the primary Australian WTP reference value of AU$ 50,000 per QALY gained. However, affordability depends on treatment eligibility, uptake, treatment duration, and acquisition costs, highlighting the need to consider budget impact alongside cost-effectiveness evidence when informing reimbursement and implementation decisions.