Targeted therapy erdafitinib (Balversa, Janssen) demonstrated a 40% response rate and was well tolerated in patients with metastatic bladder cancer marked by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene, according to results from a phase 2 study.
 
The findings, which were published in the New England Journal of Medicine, supported the FDA approval of erdafitinib in April for this patient population. The FGFR inhibitor is the first targeted therapy approved for this indication.
 
For the study, a total of 99 patients with metastatic or surgically unresectable urothelial cancer and verified mutations in the FGFR3 gene received a median of 5 cycles of erdafitinib. According to the data, the confirmed response rate to erdafitinib therapy was 40%. Erdafitinib also showed a response rate of 59% among 22 patients who had undergone previous immunotherapy. Three patients had complete responses and 39% had stable disease.
 
Additionally, the median duration of progression-free survival was 5.5 months and the median duration of overall survival was 13.8 months, according to the results.
 
Forty-six percent of patients reported treatment-related adverse events of grade 3 or higher, which were managed mainly by dose adjustments. Thirteen percent of the patients discontinued treatment because of adverse events.
 
“With a response rate of over 50% in patients previously treated with immunotherapy, the data suggest treatment with erdafitinib may be preferential for patients with FGFR3 mutations,” lead study author Arlene Siefker-Radtke, MD, professor of genitourinary medical oncology, said in a press release. “However, this is preliminary evidence, so we need additional data to confirm this finding.”
 
According to the researchers, the findings are especially important considering the need for alternative treatment options in this patient population. Although immune checkpoint inhibitors have been approved for advanced bladder cancer, only 15% to 20% of patients will benefit from these therapies, they noted.
 
“With the recent approval of erdafitinib for the treatment of patients with FGFR3-mutant urothelial cancers, we now have an additional agent to add to our armamentarium,” Dr Siefker-Radtke said. “My hope is we will be able to add this to our treatment strategy, learn how it combines with immunotherapy and how we can use the effects of this drug to improve the survival for all of our bladder cancer patients.”
 
Erdafitinib was approved in April 2019 for locally advanced or metastatic urothelial cancers with mutations in the FGFR2 or FGFR3 genes. Currently, a phase 3 trial is underway to evaluate the efficacy of erdafitinib compared with chemotherapy or the checkpoint blockade inhibitor pembrolizumab in this patient population as well.  
 
References
 
Loriot Y, Necchi A, Hoon Park S, et al. Erdafitinib in locally advanced or metastatic urothelial carcinoma. New England Journal of Medicine. 2019. Doi: 10.1056/NEJMoa1817323
 
Targeted therapy erdafitinib effective for patients with advanced bladder cancer and specific gene mutations [news release]. MD Anderson Cancer Center. https://www.mdanderson.org/newsroom/targeted-therapy-erdafitinib-effective-for-patients-with-advanced-bladder-cancer-and-specific-gene-mutations.h00-159304623.html. Accessed July 25, 2019.