Newly Approved Targeted Therapy Paves the Way for Patients With Advanced Bladder Cancer

Patients with advanced bladder cancer and a specific gene mutation have a promising new treatment option, according to phase 2 study findings published in the New England Journal of Medicine.

The international trial was led by researchers from The University of Texas MD Anderson Cancer Center and included 99 patients with metastatic urothelial carcinoma or tumors that were not able to be removed via surgery. In addition, patients had alterations in the FGFR3 gene.

Mutations in FGFR3 are present in approximately 15% to 20% of patients with metastatic bladder cancer and up to 35% of patients with other urothelial cancers, according to a press release.

“FGFR3 is found on the surface of tumors cells and when it is stimulated it causes these tumor cells to proliferate and grow in a more rapid fashion,” Dr. Arlene O. Siefker Radtke, a professor in the Department of Genitourinary Medical Oncology at MD Anderson, said in an interview with CURE®. “We can now target this with [Balversa (erdafitinib)], a small molecule that binds in that active area of the receptor and it turns that receptor off, so it no longer causes the tumor cells to proliferate. In addition, this appears to kill cancer cells as well.”

In patients with FGFR3 mutations, Balversa, an oral, targeted therapy known as a tyrosine kinase inhibitor, was well tolerated and showed an overall response rate of 40%, meaning that these patients saw their tumors shrink or disappear after therapy. The median overall survival was 13.8 months.

“The most significant finding of this study is that this is first targeted therapy approved for urothelial cancer,” Siefker Radtke said. “It is the first oral agent and the first agent based on mutation status. A median overall survival of 13.8 months is very encouraging compared to previous clinical trials with taxanes in this setting.”

In addition, three patients’ tumors disappeared completely and 39% had stable disease. The median progression-free survival, or the time following therapy in which a patient’s disease did not worsen, was 5.5 months.

The drug also proved to be a potential option for patients who previously failed immunotherapy. Of 22 patients, tumors shrank or disappeared in 13 (59%) of them.

Since it is an oral medication, patients can take it at home. However, gastrointestinal side effects are most common, such as poor appetite, nausea and upset stomach. Patients may also see changes to their skin (peeling of the skin or cracking of nails) or hair color. An infrequent side effect is central serous retinopathy, which could cause vision impairment.

“Before erdafitnib, the standard of care was frontline platinum-based chemotherapy and, if patients failed that, second-line treatment with a checkpoint inhibitor,” Siefker Radtke said. “After that, perhaps single agent taxanes, but the response rates and survival were quite poor. The treatment options are currently very limited. And that’s why it’s so exciting to have another class of agents approved for the treatment of urothelial cancer.”

Two clinical trials are currently underway to help confirm the benefits in patients — THOR and NORSE.

“The field of bladder cancer is more hopeful today than it ever has been in the past,” Siefker Radtke said. “As we begin to understand bladder cancer and the different types of bladder cancer, we are really learning that it is no longer just one disease. Once we determine which disease it is, we will be able to best select the most appropriate treatment for it.”