Editor’s Note: For many years, platinum-based chemotherapy has been the cornerstone of systemic treatment for advanced urothelial cancer, such as bladder cancer. However, the release of clinical research data on antibody-drug conjugates (ADC), such as enfortumab vedotin (EV), has brought new treatment options for patients. During the 31st Urology Academic Conference held recently in Tianjin, Dr. Xin Yao from Tianjin Medical University Cancer Institute and Hospital shared insights on “Focusing on Drug Safety Management in the Era of Combined Targeted and Immunotherapy.” After the session, Urology Frontier invited Professor Yao to discuss the value of combined targeted and immunotherapy in treating urothelial cancer and the management strategies for ensuring treatment safety.

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Urology Frontier: Research like EV-302 is ushering advanced urothelial cancer into the era of combined targeted and immunotherapy. How do you view the value of targeted therapies?

Dr. Xin Yao: In the clinical treatment of urothelial cancer, the findings from the EV-302 study undoubtedly represent a groundbreaking milestone. First, since Sternberg proposed M-VAC as the standard treatment for advanced bladder cancer in 1989, the field has waited 35 years to witness the emergence of a new first-line recommended treatment—the combination of EV and immunotherapy, as outlined in the EV-302 study. From the perspective of standardized treatment guidelines, this is a landmark event.

Second, compared with traditional chemotherapy, ADC combined with immunotherapy shows a higher response rate and significantly prolongs patient survival time. What’s even more important is that, in terms of safety, the clinical studies on EV and domestic ADCs like RC48 have demonstrated that these combined therapies are safer than cisplatin-based chemotherapy. This is not only reflected in objective data but also in patients’ improved treatment experiences and satisfaction. Therefore, I believe the approval of ADCs like EV marks the transition of advanced urothelial cancer treatment from the era of chemotherapy into the era of ADCs, opening a new chapter in treatment.

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Urology Frontier: In the era of combined targeted and immunotherapy, how should safety management be conducted to ensure patients derive more benefits?

Dr. Xin Yao: In most cases, ADCs are used in combination with immunotherapy. First, compared to traditional chemotherapy regimens, this combined approach has a lower incidence of adverse events (AEs). Second, the rate of grade 3 or higher adverse reactions is also lower than that of chemotherapy.

However, this does not mean that the safety management of ADC therapy can be overlooked. Based on our practical experience, chemotherapy patients tend to experience adverse reactions early in treatment, such as nausea, vomiting, and bone marrow suppression. In contrast, adverse events related to ADCs often occur four or five months after treatment initiation. Therefore, during the treatment process, we must remain vigilant and closely monitor and follow up with patients. Just because a patient appears safe and shows no obvious discomfort during the first two or three months of treatment does not mean we can relax our management of potential later adverse events.

Dr. Xin Yao Professor and Director of Urology, Tianjin Medical University Cancer Institute and Hospital PhD Supervisor Board Member, Chinese Anti-Cancer Association (CACA) Chair-Elect, Urologic Oncology Committee, CACA Board Member, Chinese Society of Clinical Oncology (CSCO) Chair-Elect, CSCO Kidney Cancer Committee Vice Chair, CSCO Urothelial Cancer Committee Board Member, Chinese Urological Association Chair, Urothelial Cancer Guideline Writing Group, Chinese Anti-Cancer Association Vice Chair, Kidney Cancer Guideline Writing Group, Chinese Medical Association Chair, Urologic Oncology Committee, Tianjin Anti-Cancer Association Editorial Board Member for multiple journals, including Chinese Journal of Urology, Chinese Journal of Endocrine Surgery, Journal of Robotic Surgery, Chinese Journal of Clinical Oncology, and Journal of Minimally Invasive Urology.