The importance of tissue testing
Erdafitinib’s approval and potential impact on response rate and survival highlight why it’s increasingly important for patients to have their tumor tissues tested, according to Dr. Siefker-Radtke.
“In the phase II trial [N Engl J Med 2019; 381:338-48], the response rate was about 40% in patients with FGFR-altered tumors, and overall median survival was about 13.8 months,” said Dr. Siefker-Radtke, who led the phase II trial.
In a group of patients who have progressed despite chemotherapy, that’s a promising result and provides patients an opportunity for an additional treatment if they have an FGFR3 alteration, Dr. Siefker-Radtke said.
It’s important to test patients with incurable bladder cancer when they are first diagnosed with stage 4 disease because obtaining the tissue takes time, Dr. Siefker-Radtke said.
“Knowing the presence of this mutation early allows patients to either participate in clinical trials of oral agents targeting FGFR3 or even consider some combination strategies for targeting FGFR3,” she said.
The bigger picture
FGFR3 is among the early targets identified in bladder cancer. About 60% of patients with low-grade, low-stage bladder cancer are thought to have FGFR3 alterations. And the prevalence of these alterations is estimated to be from 15% to 20% in patients with stage 4 urothelial bladder tumors, Dr. Siefker-Radtke said.
“This may actually be higher in urothelial tumors of the renal pelvis where the presence of these mutations has been reported as high at 35%,” she said.
Patients with upper urinary tract cancer have even fewer treatment options and less definitive data from clinical trials. If the trial data on erdafitinib in patients with upper tract tumors does pan out, “that’s a real need that could be filled by this drug,” Dr. Konety said.
Dr. Siefker-Radtke said testing for FGFR3 mutations in advanced bladder cancer patients is top priority when she is testing for mutations.
“Following that, there is more limited data on the need for additional testing,” she said. “There is some data that if a patient is not eligible for cisplatin and their tumors are PD-L1 high, then they might benefit from a single-agent immune checkpoint inhibitor. So, that would be the second marker that I would consider testing, but only in patients who haven’t had prior chemotherapy for their stage 4 disease,” Dr. Siefker-Radtke said.
The FDA has approved several checkpoint inhibitors for advanced bladder cancer, but only about one in five patients benefit from these agents, according to Dr. Siefker-Radtke.
Promising novel agents are targeting other pathways, including the human epidermal growth factor receptor 2 (HER2) pathway and mammalian target of rapamycin (mTOR) pathway, but trials looking at those pathways in the setting of bladder cancer have not yet demonstrated strong benefit, Dr. Lotan said.
“There have been rare patients who have had success from other targeted therapies. But no other targeted therapy has been uniformly approved for patients with bladder cancer,” he said.