Testing Combinations in Metastatic Urothelial Cancer

The future of metastatic urothelial cancer is in combination therapy, according to Dr. Nancy B. Davis.

New therapies, such as Balversa (erdafitinib), Padcev (enfortumab vedotin-ejfv) and sacituzumab govitecan, have shown promise when used alone to treat patients with advanced disease. But now researchers hope to examine how well they work when combined with other types of medications like immunotherapies, and earlier in the treatment process.

“We're going to see erdafitinib or other FGFR inhibitors combined with immunotherapy,” Davis, associate professor of medicine in the division of hematology/oncology at Vanderbilt-Ingram Cancer Center in Nashville, said in an interview OncLive®, a sister publication of CURE®.

Roughly 10%-15% of patients with urothelial cancer have an FGFR mutation. By targeting this mutation with specific therapies, it could improve patient survival outcomes.

“We’re currently (sending genetic testing) for every patient with metastatic disease,” Davis said. “It probably needs to be done earlier for patients with muscle-invasive disease as we learn more about these drugs.” She added: “In oncology, we always (test agents in the) metastatic setting (and evaluate them in the) first-line setting. In urothelial cancer, the next question will be whether erdafitinib (is effective) in the frontline setting, and if so, whether it will work in the neoadjuvant setting.”

Balversa, the first targeted therapy for metastatic bladder cancer, was approved by the Food and Drug Administration (FDA) in April 2019 to treat adult patients with FGFR mutations. “(This agent) is very exciting for patients who have the mutation,” she said. “The mutation tends to occur earlier in the development of disease.”

However, Balversa can only be used as a second or later therapy. Since these patients don’t respond well to platinum-based therapies or immunotherapy, it’s important to see if it can be moved to an upfront treatment, explained Davis.

Another treatment option for adults with locally advanced or metastatic urothelial cancer is Padcev, which was FDA-approved in December 2019. A phase 2 clinical trial showed that patients given the medication had a 44% overall response rate. The drug targets Nectin-4, which is a protein expressed in more than 80% of bladder cancers. Experts hope to study this in earlier treatment settings, too.

Side effects of Padcev include neuropathy, nausea, vomiting and diarrhea.

Still in investigational stages, sacituzumab govitecan is more like a chemotherapy-medication, explained Davis. There is currently an ongoing phase 2 clinical involving two groups of patients who have already had immunotherapy-based therapies and were platinum ineligible. Sacituzumab govitecan binds to TROP2 — a cell surface antigen that is highly expressed in bladder cancer. “The data are early, but they’re exciting,” said Davis.

This article was adapted from an article that originally appeared on OncLive, titled “Assessing Long-Anticipated Treatment Advances in Metastatic Urothelial Cancer.”