July 25, 2019
3 min read

Erdafitinib appears effective for locally advanced, metastatic urothelial carcinoma

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Arlene Siefker-Radtke

Erdafitinib induced a high rate of objective tumor response among patients with locally advanced and unresectable or metastatic urothelial carcinoma with FGFR alterations, according to results of a single-arm phase 2 study published in The New England Journal of Medicine.

Erdafitinib (Balversa; Janssen, Astex Therapeutics) — a tyrosine kinase inhibitor of FGFR — received FDA accelerated approval in April based on these data, becoming the first targeted therapy approved for bladder cancer.

“Patients have been in desperate need for alternative strategies, especially when a large number of patients cannot tolerate the current standards of care,” Arlene Siefker-Radtke, MD, professor of genitourinary medical oncology at The University of Texas MD Anderson Cancer Center, said in a press release. “We were very gratified to see a 40% response rate in patients treated on this clinical trial. Not only did it work well in patients with lymph node metastases, but also in patients with high-volume and very aggressive disease.”

Chemotherapy with taxanes or vinflunine is historically associated with an objective response rate of 10% and a median OS of 7 to 9 months. Checkpoint inhibitors have improved response rates to the range of 13% to 21%, with a median OS of 10.3 months.

Erdafitinib demonstrated antitumor activity in a phase 1 study involving patients with urothelial carcinoma and other tumor types with FGFR alterations.

For the study, Siefker-Radtke and colleagues enrolled 99 patients (median age, 68 years; range, 36-87) with locally advanced and unresectable or metastatic urothelial carcinoma with FGFR alterations.

All patients had a history of disease progression during or after a prior course of chemotherapy or within 12 months of neoadjuvant or adjuvant chemotherapy. Forty-three percent of patients had previously received at least two courses of treatment, 53% had creatinine clearance of less than 60 mL/min and 79% had visceral metastases.

Patients received 8 mg erdafitinib in a continuous regimen (n = 58) or 8 mg with a guided dose escalation to 9 mg (n = 41) for a median of five cycles (range, 1-18).

ORR served as the study’s primary endpoint. PFS, OS and duration of response served as secondary endpoints.

Median follow-up for survival was 11 months (interquartile range, 0.7-17.4).

Results showed an ORR of 40% (95% CI, 31-50) — which included a 37% partial response rate and 3% complete response rate — indicating the study met its primary endpoint. Among 22% patients who previously received immunotherapy, 59% demonstrated a response to erdafitinib.


Median duration of response was 5.6 months (95% CI, 4.2-7.2), and about 30% of the responses lasted for at least 12 months.

Median PFS among all patients was 5.5 months (95% CI, 4.2-6), with 19% (95% CI, 11-29) of patients achieving 12-month PFS. Median OS was 13.8 months (95% CI, 9.8-not reached), with a 55% (95% CI, 43-66) 12-month OS rate.

All patients experienced at least one adverse event of any grade. Grade 3 or higher adverse events deemed related to treatment occurred in 46% of patients, with 13% discontinuing treatment because of unacceptable toxicity.

Common grade 3 or higher adverse events included hyponatremia (11%), stomatitis (10%) and asthenia (7%).

“With the recent approval of erdafitinib for the treatment of patients with FGFR3-mutant urothelial cancer, we now have an additional agent to add to our armamentarium,” Siefker-Radtke said in the release. “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 [patients with bladder cancer].” – by John DeRosier

Disclosures: Janssen Pharmaceuticals funded this study. Siefker-Radtke reports advisory/consultant roles with Bavarian Nordic, EMD Serono, and Janssen. Please see the study for all other authors’ relevant financial disclosures.