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

The KEYNOTE-054 trial demonstrated that adjuvant pembrolizumab improves recurrence-free survival in completely resected stage III melanoma versus watchful waiting (hazard ratio [HR] = 0.57; 98.4% confidence interval [CI], 0.43-0.74). We evaluated the cost-effectiveness of pembrolizumab in Argentina, where watchful waiting is still widely used among these patients despite the high risk of recurrence with surgery alone. A four-health state model was used (recurrence-free, locoregional recurrence [LR], distant metastases [DM], death). Lifetime medical costs to payers (72.08 Argentine pesos [AR$] = 1.00 U.S. dollar [USD]) and outcomes (3% annual discount) were assessed, together with incremental cost-effectiveness ratios (ICERs). First and LR→DM recurrences were modeled using KEYNOTE-054 and real-world data, respectively. No benefits of adjuvant treatment were assumed post-progression. Pre-DM and post-DM mortality was based on KEYNOTE-054 and on a network meta-analysis of advanced treatments expected in each arm, respectively. Utilities were derived from KEYNOTE-054 Euro-QoL data using an Argentinian algorithm, and from the literature. Public ex-factory drug prices were used. Patients in the pembrolizumab and the watchful waiting arms accrued 8.78 and 5.83 quality-adjusted life-years (QALYs), 9.91 and 6.98 life-years, and costs of AR$12,698,595 (176,174 USD) and AR$11,967,717 (166,034 USD), respectively. The proportion of life-years accrued that were recurrence-free was 80.8% and 56.9% in the pembrolizumab and the watchful waiting arms, respectively. Pembrolizumab patients gained 2.94 life-years and 2.96 QALYs versus watchful waiting; the ICER per QALY was AR$247,094 (3428 USD). Recurrence rates and advanced melanoma treatments were the key drivers of the ICER. At a threshold of AR$1,445,325 (29,935 USD) per QALY, pembrolizumab had an 83.5% probability of being cost-effective versus watchful waiting. Adjuvant pembrolizumab after complete resection of melanoma with node involvement is highly cost-effective relative to watchful waiting in Argentina, across disease stage subgroups and BRAF mutational status. This strongly supports its coverage and reimbursement across the entire health system.