Platinum-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.
We 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).
Our analysis encompassed 3 RCTs, involving 2162 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 < .01), progression-free survival (HR 0.78; 95% CI 0.70-0.86; P < .01), and objective response rate (RR 1.20; 95% CI 1.06-1.36; P < .01), while elevating the risk of immune-related adverse events (P-value = .02).
In 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.
Clinical genitourinary cancer. 2024 Jul 11 [Epub ahead of print]
Isadora Mamede, Lorena Escalante-Romero, Davi S Gonçalves Celso, Pedro C Abrahao Reis, Maria Inez Dacoregio, Ana Caroline Alves, Carlos Stecca
Department of Medicine, Federal University of Sao Joao del-Rei, Divinopolis, Minas Gerais 35501-296, Brazil. Electronic address: ., Department of Pediatric Oncology, Federal University of Sao Paulo, Sao Paulo, Sao Paulo 04021-001, Brazil., Department of Medicine, Federal University of Vicosa, Vicosa, Minas Gerais 36570-900, Brazil., Department of Medicine, Federal University of Rio de Janeiro, Rio de Janeiro, Rio De Janeiro 21044-020, Brazil., Department of Medicine, Universidade Estadual do Centro Oeste-UNICENTRO, Guarapuava, Parana 85015-430, Brazil., Department of Clinical Oncology, Sao Domingos Hospital/DASA, Sao Luis, Maranhao 65060-645, Brazil., Department of Clinical Oncology, Mackenzie Evangelical University Hospital, Curitiba, Parana 80730-150, Brazil.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/39094286