The authors selected four articles (n = 3340 patients) based on the following inclusion criteria: AMUC patients, comparison between carboplatin- or cisplatin-based chemotherapy versus immunotherapy, first-line treatment, evaluation of survival outcomes, and phase 3 randomized study. Three of these studies were randomized controlled trials (RCTs) in which first-line immune checkpoint inhibitor (ICI) therapy was compared with carboplatin- and cisplatin-based chemotherapy. These studies were the DANUBE study, the IMvigor130 study, and the KEYNOTE-361 study. Among all patients across the three studies, the proportion of patients with high PD-L1 expression varied between 24% and 60%. In the last RCT, outcomes were compared between patients receiving carboplatin and cisplatin-based chemotherapy.
Analysis revealed that OS was not significantly different between cisplatin- or carboplatin-based chemotherapy and ICI therapy. However, there was a significantly higher objective response rate (ORR) among patients receiving cisplatin-based chemotherapy or carboplatin-based chemotherapy versus ICI monotherapy (p < 0.001). When all three treatment types were compared in a network meta-analysis, with ICI therapy as the common reference, there was no significant difference in OS, CR, or ORR between carboplatin-based and cisplatin-based chemotherapy. Cisplatin has slightly higher OS, CR, and OR than carboplatin, but the differences were not statistically significant.
This meta-analysis provides additional confidence to the growing body of evidence supporting a lack of difference in clinical outcomes of carboplatin-based versus cisplatin-based chemotherapy in patients with advanced urothelial carcinoma. However, the authors maintain that there were slight differences between the trial designs that could affect the outcome. For instance, more patients in the KEYNOTE-361 trial received ICI therapy after chemotherapy than in the other trials. This may lead to more favorable OS that is not representative of chemotherapy alone. Moreover, a direct comparison between carboplatin- and cisplatin-based chemotherapy would have been more informative than comparing each to ICI.
Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine
Reference:
- Mori K, Schuettfort VM, Yanagisawa T, et al. Reassessment of the Efficacy of Carboplatin for Metastatic Urothelial Carcinoma in the Era of Immunotherapy: A Systematic Review and Meta-analysis. Eur Urol Focus. 2022;8(6):1687-1695.