Immunotherapy plus chemotherapy versus chemotherapy alone as first-line treatment for advanced urothelial cancer: an updated systematic review and meta-analysis of randomized controlled trials

Abstract

IntroductionPlatinum-based chemotherapy (CTX) has historically been the primary treatment for advanced urothelial cancer (aUC), with limited alternative options. The therapeutic landscape experienced a paradigm shift following the results of the EV-302 and Checkmate-901 trials, which led to the approval of Enfortumab vedotin plus pembrolizumab (EV-P) as the preferred first-line treatment, and nivolumab plus CTX for those unable to receive the preferred regimen. Currently, further investigations are underway to explore PD-1 and PD-L1 inhibitors in the initial treatment of aUC. Patients and MethodsWe conducted a systematic search across PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) comparing immune checkpoint inhibitors (ICI)-CTX combinations versus CTX alone as first-line treatment for advanced UC. Employing a random-effects model, we pooled hazard ratios (HR) with 95% confidence intervals (CI). ResultsOur analysis encompassed five RCTs, involving 2,162 participants, with 51.16% randomized to combination therapy with platinum-based CTX. Compared to CTX alone, immune-chemotherapy significantly improved overall survival (HR 0.84; 95% CI 0.75-0.93; p < 0.01), progression-free survival (HR 0.78; 95% CI 0.70-0.86; p < 0.01), and objective response rate (RR 1.20; 95% CI 1.06-1.36; p < 0.01), while elevating the risk of immune-related adverse events (p-value = 0.02). ConclusionIn this meta-analysis of RCTs, ICI plus CTX demonstrated a significant association with improved survival at the expense of an increased risk of immune-related adverse events. Therefore, our findings suggest that this combination should be considered as an initial treatment for aUC in platinum-eligible patients who cannot receive EV-P. Micro abstractThis meta-analysis investigates immune checkpoint inhibitors (ICI) combined with platinum-based chemotherapy (CTX) as a first-line treatment for advanced urothelial cancer (aUC). Analyzing data from three randomized controlled trials with 2,162 patients, the study demonstrates that ICI-CTX improve overall survival, progression-free survival, and response rates. These findings support the consideration of ICI-CTX as an initial treatment option for platinum-eligible aUC patients.