The "One-to-Many" Survival Analysis to Evaluate a New Treatment in Comparison With Therapeutic Alternatives Based on Reconstructed Patient Data: Enfortumab Vedotin Versus Standard of Care in Advanced or Metastatic Urothelial Carcinoma

Abstract

Objective This paper presents a preliminary experience based on the "one-to-many" approach of the Shiny method. Numerous (or "many") treatments for advanced or metastatic urothelial carcinoma have recently been reviewed. More recently, "one" potentially innovative treatment has been made available. Our analysis was aimed at assessing the benefits of the new treatment in comparison with the alternatives developed previously. Materials and methods The Shiny method was employed to reconstruct patient-level survival data. This information allowed us to compare the Kaplan-Meier (KM) curves of five treatments previously available (i.e., pembrolizumab, nivolumab, atezolizumab, vinflunine, and standard chemotherapy) with the potentially innovative agent represented by enfortumab vedotin. Overall survival was evaluated for each agent. Statistical tests to assess head-to-head indirect comparisons were performed through standard survival analysis. The hazard ratio (HR) was the main parameter. Results In ranking the efficacy across these agents, enfortumab vedotin was first, followed by immune checkpoint inhibitors (ICIs). Standard chemotherapy and vinflunine were the least effective. The remarkable survival results of enfortumab were, to some extent, influenced by the slightly better prognosis of the population enrolled in the enfortumab trial in comparison with patients enrolled in the three ICI trials. Conclusions The experience described herein shows that, when a potential innovative treatment (enfortumab vedotin) is developed in an already investigated area (metastatic urothelial cancer), the Shiny method can be applied according to the "one-to-many" approach. This allows us to quickly assess the place in therapy of the new treatment (the "one") and to evaluate whether the new treatment determines a relevant incremental benefit in comparison with previous treatments (the "many").

Keywords: artificial intelligence; indirect comparisons; metastatic urothelial carcinoma; reconstruction of patient-level data; survival analysis.