Abstract
Introduction A combination of ipilimumab/nivolumab has demonstrated a median overall survival (mOS) of 71.9 months in advanced melanoma, establishing it as the standard first-line (1L) therapy. However, the approval of this combination by the Portuguese Regulatory Authority occurred 76 months after its approval by the European Authority, leaving tyrosine kinase inhibitors as the only 1L option available for the BRAF-mutated melanoma population. Our study aims to evaluate real-world data from patients with advanced melanoma and assess the potential prognostic impact of the delayed availability of ipilimumab/nivolumab combination therapy on this population. Methods This was an observational, retrospective cohort study conducted at a Portuguese Comprehensive Cancer Center. The study included adult patients with melanoma who received innovative therapies in the 1L between May 2016 and December 2021 and who would meet the criteria for treatment with ipilimumab/nivolumab. The primary outcome measure was mOS; secondary outcome measures included median progression-free survival (mPFS), objective response rate (ORR), and safety data. Results Our study included 172 patients, of which 50% were male, and 32.6% (n = 56) had BRAF-mutated melanoma. In 1L setting, 70.9% received anti-programmed cell death protein 1 (anti-PD-1) monotherapy, while the rest were treated with targeted therapies. The median follow-up time was 57 months. Patients treated with anti-PD-1 had ORR of 36.0%, mPFS of seven months (95% CI 2.9-11.1), and mOS of 19 months (95% CI 7.5-30.4). Among patients treated with targeted therapies, the ORR was 56.0%, mPFS seven months (95% CI 5.1-8.9), and mOS 14 months (95% CI 5.9-22.1). In our population, 10% presented grade 3 or higher adverse events, with no drug-related deaths reported. Conclusion These findings underscore significant disparities in access to innovative therapies in Portugal, which may have adversely impacted patients' outcomes. The delay raises ethical concerns regarding equity in healthcare access and highlights the need for policy measures to expedite the approval and availability of life-extending treatments.