Comparative efficacy and safety of prolgolimab and nivolumab in first-line therapy for metastatic or unresectable melanoma: a systematic review, matching-adjusted indirect comparison, and cost-effectiveness analysis

Vollständiger Abstract

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Background . Metastatic and unresectable cutaneous melanoma (MM/uRCM) is an aggressive malignancy associated with high mortality due to its pronounced metastatic potential. Immune checkpoint inhibitors are used to treat MM/uRCM in the Russian Federation. These inhibitors include nivolumab and prolgolimab, which block the programmed cell death 1 (PD-1) receptor. However, there are no direct comparative data on their clinical and economic efficacy and safety as monotherapy, which complicates optimal therapeutic decision-making. Objective : To evaluate the clinical efficacy and safety of prolgolimab versus nivolumab in MM/uRCM treatment and to conduct cost-effectiveness analysis based on data obtained. Material and methods. A systematic literature search was conducted in the Embase and PubMed/MEDLINE databases, which identified four clinical trials of prolgolimab and nivolumab in first-line therapy for MM/uRCM. The results were used to perform a matchingadjusted indirect comparison (MAIC) without an anchor. Cox regression and logistic regression were applied for the efficacy and safety analyses, respectively. A cost minimization analysis was carried out using the weight characteristics of 743 Russian patients with MM/uRCM. The analysis only considered the costs of drug therapy. Additionally, the costs of treatment with comparator drugs were evaluated in real-world clinical setting, taking into account therapy discontinuation due to disease progression or patient death. A budget impact analysis was performed for 10 patients with MM/uRCM. Results . In MAIC, the prolgolimab monotherapy showed no statistically significant differences in overall survival compared to nivolumab after population balancing: hazard ratio (HR) 0.84 (95% confidence interval (CI) 0.47–1.50; p=0.557) in CheckMate 067 trial population; HR 0.89 (95% CI 0.53–1.49; p=0.649) in RELATIVITY-047 trial population. Similarly, for progression-free survival: HR 1.14 (95% CI 0.77–1.70; p=0.511) for CheckMate 067; HR 1.07 (95% CI 0.77–1.48; p=0.683) for RELATIVITY-047. Based on cost minimization analysis results, weighted average annual drug therapy costs for the Russian patient population were 3.98 million rubles for prolgolimab, compared to 5.33 million rubles for nivolumab (34% higher). First-year therapy costs accounting for gradual discontinuation due to progression and death were 2.39 million rubles for prolgolimab versus 3.2 million rubles for nivolumab (difference: 809,559 rubles; 34%). On a five-year horizon, total drug therapy costs were 6.16 million rubles for prolgolimab and 8.25 million rubles for nivolumab. Budget impact analysis revealed a difference in therapy costs for 10 patients with MM/uRCM over a 1-year and 5-year horizons of 13.47 and 20.84 million rubles, respectively. Due to the cost difference, an additional three patients can be treated within the analyzed timeframe. Conclusion . Prolgolimab monotherapy demonstrated no statistically significant differences in overall survival or progression-free survival compared with nivolumab in MAIC. Given its comparable clinical efficacy and lower cost per treatment course, prolgolimab is cost-effective within the Russian healthcare system and allows for increased patient coverage without additional budget expenditures.