Despite recent developments in the landscape of urothelial carcinoma (UC) treatment, platinum combination chemotherapy still remains a milestone. Recently immunotherapeutic agents have gained ever-growing attractivity, particularly in the metastatic setting. Novel chemotherapeutic strategies and agents, such as antibody-drug conjugates (ADCs), and powerful combination regimens have been developed to overcome the resistance of most UC to current therapies.
Herein, we review the current standard-of-care chemotherapy, the development of ADCs, the rationale for combining therapy regimens with chemotherapy in current trials, and future directions in UC management.
Immunotherapy has prompted a revolution in the treatment paradigm of UC. However, only a few patients experience a long-term response when treated with single-agent immunotherapies. Combination treatments are necessary to bypass resistance mechanisms and broaden the clinical utility of current options. Current evidence supports the intensification of standard-of-care chemotherapy with maintenance immunotherapy. However, the optimal sequence, combination, and duration must be determined to achieve individual longevity with acceptable health-related quality of life. In that regard, ADCs appear as a promising alternative for single and combination strategies in UC, as they specifically target the tumor cells, thereby, theoretically improving treatment efficacy and avoiding extensive off-target toxicities.
Expert opinion on pharmacotherapy. 2022 Nov 28 [Epub ahead of print]
Alberto Bianchi, Markus von Deimling, Maximilian Pallauf, Takafumi Yanagisawa, Tatsushi Kawada, Hadi Mostafaei, Fahad Quhal, Ekaterina Laukhtina, Pawel Rajwa, Muhammad Majdoub, Reza Sari Motlagh, Benjamin Pradere, Pierre I Karakiewicz, Maria Angela Cerruto, Alessandro Antonelli, Shahrokh F Shariat
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada., Department of Urology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.