The fibroblast growth factor receptor (FGFR) inhibitor erdafitinib (Balversa) showed promising antitumor activity in patients with advanced urothelial carcinoma, according to a recent phase 2 trial published in the New England Journal of Medicine.
Urothelial carcinoma, also known as transitional cell carcinoma (TCC), is one of the most common type of bladder cancer. The cancer starts in the urothelial cells that line the inside of the bladder.
The study revealed antitumor activity of erdafitinib in urothelial carcinoma with alterations in the FGFR3 gene, yielding a 40% overall response rate (ORR).
An international group of researchers evaluated 99 patients with locally advanced and unresectable or metastatic urothelial carcinoma who had disease progression on or after at least one course of chemotherapy, or within 12 months after neoadjuvant/adjuvant therapy.
Patients were treated with 8 or 9 mg of erdafitinib, depending on their phosphate level, until their disease progressed or they experienced unacceptable adverse events (AEs).
The 40% ORR consisted of a 3% complete response (CR) rate and a 37% partial response (PR) rate. Among 22 patients in whom immunotherapy had failed, 59% had a CR or PR. At a median follow-up of 11.2 months, the median duration of progression-free survival was 5.5 months (95% CI, 4.2-6 months). At a median follow-up of 11 months, the median duration of overall survival was 13.8 months (95% CI, 9.8 months to not reached).
The response rates were similar regardless of patients’ history of chemotherapy, courses of treatment, presence of visceral metastases or baseline characteristics.
“The data suggest treatment with erdafitinib may be preferential for patients with FGFR3 mutations,” which are present in approximately 15% to 20% of patients with metastatic bladder cancer and 35% of patients with other urothelial cancers, said the lead investigator Arlene Siefker-Radtke, MD, Professor of Genitourinary Medical Oncology at the University of Texas MD Anderson Cancer Center, Houston.
“It was notable that we observed objective responses even in patients with visceral metastases and in a group of patients who were heavily pretreated with poor kidney function, who typically have a very poor prognosis,” told Siefker-Radtke, to Clinical Oncology News.
“Further work is needed to determine whether these FGFR3-altered urothelial tumors benefit more from treatment with erdafitinib as compared to immune checkpoint inhibition,” she said.
Phase 3 Thor trial has been “developed to answer this question by randomizing patients treated with prior chemotherapy to either erdafitinib or an immune checkpoint inhibitor.”
In addition, she said, the Norse trial, which is currently recruiting, combines erdafitinib with an immune checkpoint inhibitor to see whether it can enhance the response rate or durability of response through combination therapy.
The researchers hope to add erdafitinib to the treatment strategy, to evaluate how it combines with immunotherapy and how the effect of the drug can improve the survival for bladder cancer patients.