Platinum-based chemotherapy has been the standard first-line (1L) treatment for advanced urothelial carcinoma (UC) for decades, based on the proven efficacy and established safety profiles of cisplatin- and carboplatin-based regimens. With the emergence of novel regimens, it is important to reevaluate and contextualize the role of 1L platinum-based chemotherapy. Platinum-based chemotherapy followed by avelumab 1L maintenance in patients without disease progression following platinum-based chemotherapy was established as a standard 1L regimen based on the JAVELIN Bladder 100 phase III trial. More recently, the EV-302 phase III trial showed the superiority of 1L enfortumab vedotin (EV) + pembrolizumab versus platinum-based chemotherapy, and the Checkmate 901 phase III trial showed the superiority of 1L nivolumab + cisplatin/gemcitabine versus cisplatin/gemcitabine alone. These 2 regimens have now been included as standard 1L options in treatment guidelines for advanced UC. EV + pembrolizumab is now the preferred 1L treatment, and in locations where EV + pembrolizumab is not available or individual patients are not considered suitable, recommended options are platinum-based chemotherapy followed by avelumab maintenance or nivolumab + cisplatin-based chemotherapy. In this review, we discuss current treatment options for advanced UC recommended in guidelines, practical considerations with platinum-based chemotherapy, the role of avelumab 1L maintenance, recent phase III trials of EV + pembrolizumab and nivolumab + cisplatin/gemcitabine, safety profiles of recommended 1L treatments, and second-line treatment options.
The oncologist. 2024 Aug 21 [Epub ahead of print]
Tian Zhang, Alan Tan, Amishi Y Shah, Gopa Iyer, Valerie Morris, Sébastien Michaud, Srikala S Sridhar
Department of Internal Medicine, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, United States., Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States., Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, United States., EMD Serono, Inc., Rockland, MA, United States, an affiliate of Merck KGaA., Princess Margaret Cancer Center, University of Toronto, Toronto, Ontario, Canada.