Disease Progression After Maintenance Therapy for Locally Advanced or Metastatic UC

Jeanny B. Aragon-Ching, MD, FACP, Clinical Program Director of Genitourinary Cancers at Inova Schar Cancer Institute, describes the available treatment options for patients with locally advanced or metastatic urothelial carcinoma who progress on avelumab maintenance.

Dr. Aragon-Ching: So, this is also an area of where a lot of clinical trials are ongoing now, but for standard of care, we always want to know what their genomic sequencing status is of the tumor. So this is also an area where the knowledge or know-how about the genomic sequencing of their tumors matter. For instance, if they have, let’s say, sequencing results that show FGFR alteration, then we can use erdafitinib, which is an FGFR inhibitor, for instance, but that would capture probably only about 20% of patients because not all patients would harbor a mutation that you can target. So for the rest of the patients, we have currently two standard of care options in terms of ADC, so that’s antibody drug conjugates.

So one is enfortumab vedotin, I just shorten it to EV. Another one is sacituzumab, which is SG. So both of them are ADCs, so antibody drug conjugates, so they’re not really similar to immunotherapy and not really similar to chemotherapy, but I would say probably a little more similar to chemo because there’s a payload and there’s an antibody target. So meaning EV, for instance, the target is nectin-4, whereas SG, the target is TROP-2. So once you deliver the drug, what it’ll do is seek out the antigen and once it binds to, it will release the payload that is a chemotherapy equivalent, if you will. So it’s more a targeted therapy or treatment in a way, and they are both approved in patients with metastatic urothelial cancer.

Typically after progression from prior standard of care treatment. So for instance, a patient who has seen chemotherapy followed by avelumab maintenance now is progressing. So that would be sort of the next line of therapy, and understanding the side effect profile of each of these drugs also matters. So for instance, if you have someone who is a brittle diabetic, have high blood sugar, EV would require a lot of monitoring because hyperglycemia is a prominent side effect, for instance, whereas someone who has a lot of issues, frailty, of course, myelosuppression is also can be a big one with SG. So a lot of appropriate monitoring for these patients, especially in the second line and beyond treatment line setting, and again, my patient has always been clinical trials, so if there was an appropriate clinical trials for such patients, then that ought to be considered as well.

View Dr. Aragon-Ching’s other comments on locally advanced or metastatic urothelial carcinoma, including Maintenance Therapy Options, ASCO-GU Clinical Research of Interest, and The Future of Personalized Care.