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Dr. Morgans on current state and future of antibody-drug conjugates in urothelial carcinoma


Combining the approved antibody-drug conjugates with other agents in this space may provide some synergy and allow even more efficacy and disease control, explains Alicia Morgans, MD.

Alicia Morgans, MD, MPH, discusses the mechanism of action of antibody-drug conjugates (ADCs), FDA-approved ADCs for the treatment of patients with metastatic urothelial carcinoma, and future approaches, such as combination regimens, with ADCs in this space. Morgans is a member, faculty of medicine, Harvard Medical School, and medical director, Survivorship Program, Dana-Farber Cancer Institute.

Video Transcript

At this point in time, we have 2 ADCs that are approved for metastatic urothelial carcinoma, and those are enfortumab vedotin (Padcev) and sacituzumab govitecan (Trodelvy). Both of these provide a unique mechanism. They're both, of course targeted, but with different ligands that allow us to deliver these really toxic treatments directly to the cancer. So think of this as delivering chemotherapy. It is chemotherapy, essentially, but we're delivering it right to the tumor. And so that makes its toxicity profile much more manageable for our patients. And these are chemotherapies that are really things that would be too toxic to deliver without this mechanism of the antibody targeting to the cancer cells directly. And so that also gives us another exciting mechanism of action—new exciting treatments that can be very, very highly effective against urothelial carcinoma, because they're so targeted and because they are so toxic, but really mitigating that toxicity profile by targeting directly to the cancer.

So, these are the ADC options that are available now. And we also are looking forward to combinations with things like pembrolizumab (Keytruda) for both of these drugs, because that combination may provide some synergy and allow even more efficacy and disease control.

The transcript has been edited for clarity.

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