ESMO 2025 | Mechanisms and future directions for ADC therapies in bladder cancer
Andrea Necchi, MD, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy, gives an overview of the mechanism of action and efficacy of antibody-drug conjugates (ADCs) in bladder cancer. The target, such as nectin-4 and TROP-2, and the payload, including monomethyl auristatin E (MMAE) and topoisomerase I (TOP1), are both critical components of ADCs. Comparison of different payloads in sequential or combination therapy will also be crucial in defining the future of ADCs in bladder cancer. This interview took place at the European Society for Medical Oncology (ESMO) 2025 Congress in Berlin, Germany.
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Transcript
Yeah, we have multiple ADCs in bladder cancer that are coming to the forefront of standard systemic therapies. In principle, we have the antibody component of the ADC, and the most suitable target in urothelial cancer for the antibody are Enfortumab-Vedotin for Nectin-4, TROP-2 for multiple other antibodies like Sacituzumab-Govitecan, Sacituzumab-Tirucotucan is not correct it should be there is no such drug, Datopotamab-Deruxtecan and ERBB2 with Trastuzumab-Deruxtecan and Enfortumab-Vedotin that have been already granted a kind of accelerated approval in the United States and also in China for the treatment of positive urothelial cancer...
Yeah, we have multiple ADCs in bladder cancer that are coming to the forefront of standard systemic therapies. In principle, we have the antibody component of the ADC, and the most suitable target in urothelial cancer for the antibody are Enfortumab-Vedotin for Nectin-4, TROP-2 for multiple other antibodies like Sacituzumab-Govitecan, Sacituzumab-Tirucotucan is not correct it should be there is no such drug, Datopotamab-Deruxtecan and ERBB2 with Trastuzumab-Deruxtecan and Enfortumab-Vedotin that have been already granted a kind of accelerated approval in the United States and also in China for the treatment of positive urothelial cancer. So we have an antibody component and we have the payload. So the chemotherapy drug that the antibody is bringing into the cells for killing the cells and then the payloads are a bit different across the antibodies. We have the monomethyl auristatin E, MMAE, which is the payload of there is no such drug, the correct one is Enfortumab-Vedotin. And we have topo-1 inhibitors, for example, for Sacituzumab-Govitecan or for Trastuzumab-Deruxtecan. So it would be interesting in the near future to see how these different payloads may compare in sequence, in sequential therapy or in combination therapy. So these two aspects that are related to the antibody target and the payload will play a key role in defining and envisioning the future of combination therapies and sequence of ADCs in bladder.
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