Erdafitinib Urothelial Carcinoma Data Update Shows Strong Response

Arlene O. Siefker-Radtke, MD

Erdafitinib (Balversa) induced an objective response rate (ORR) of 40% in previously treated patients with locally advanced or metastatic urothelial carcinoma, according to findings from the pivotal phase II BLC2001 trial published in the New England Journal of Medicine.

Based on previously reported data from the study, the FDA approved the FGFR1-4 inhibitor erdafitinib in April 2019 for the treatment of adult patients with locally advanced or metastatic bladder cancer with an FGFR3 or FGFR2 alteration that has progressed on platinum-containing chemotherapy. The FDA action made erdafitinib the first targeted therapy approved for metastatic 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,” lead study investigator Arlene Siefker-Radtke, MD, 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.”

Also of note, the ORR was 59% in patients who had progressed after receiving immunotherapy.

“I noticed that I wasn’t seeing a great response to immune checkpoint inhibitors in my patients with FGFR3 mutations, which led me to wonder whether this would reflect a group of patients with an unmet need,” said Siefker-Radtke. “When we heard about novel agents targeting this pathway, I became quite interested in exploring them in our bladder cancer patients.”

“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. However, this is preliminary evidence, so we need additional data to confirm this finding,” said Siefker-Radtke.

The open-label, single-arm, multicenter BLC2001 trial included 99 patients with metastatic or surgically unresectable urothelial cancer with FGFR genomic alterations. As confirmed by a central laboratory, patients had FGFR3 gene mutations (R248C, S249C, G370C, Y373C) or FGFR gene fusions (FGFR3-TACC3, FGFR3-BAIAP2L1, FGFR2-BICC1, FGFR2-CASP7).

Patients had a median age of 68 years (range, 36-87), 76 were male, and 23 were female. Ninety-three percent of patients had an ECOG performance status of 0 or 1 and 79% had visceral metastases. Eighty-eight percent of patients had progressed or relapsed after chemotherapy, 12% had no prior chemotherapy, and 22% had progressed or relapsed after immunotherapy.

The starting dose of erdafitinib was 8 mg once daily. Patients whose serum phosphate levels were below the target of 5.5 mg/dL between days 14 and 17 had their dose increased to 9 mg once daily. Patients were treated until unacceptable toxicity or disease progression.

The ORR included 3 complete responses and 37 partial responses. There were 39 patients with stable disease, 18 patients with progressive disease, and 2 patients could not be evaluated.

The median duration of response was 5.6 months (95% CI, 4.2-7.2). The ORR was 49% among patients with an FGFR3 gene mutation and 16% among patients with an FGFR2/3 gene fusion. Patients receiving the 8-mg dose had an ORR of 34% and those whose dose escalated to 9 mg had an ORR of 49%. Among patients treated with 0, 1, 2, 3, and ≥4 prior systemic treatments, the ORRs were 36%, 38%, 38%, 60%, and 50%, respectively. The ORR was 42% in the group who had not received prior chemotherapy and 40% in those who had progressed or relapsed following chemotherapy. In patients with lymph node metastases only, the ORR was 33%.

The most common adverse events (AEs) across all grades were hyperphosphatemia (77%), stomatitis (58%), diarrhea (51%), dry mouth (46%), decreased appetite (38%), dysgeusia (37%), fatigue (32%), dry skin (32%), alopecia (29%), constipation (28%), and hand-foot syndrome (23%). The most common grade ≥3 AEs included hyponatremia (11%), stomatitis (10%), asthenia (7%), nail dystrophy (6%), hand-foot syndrome (5%), and urinary tract infection (5%). AEs led to treatment discontinuation in 13% of patients. There were no treatment-related deaths.

Erdafitinib was granted an accelerated approval by the FDA, meaning additional data from a confirmatory trial are needed to support a full approval.

“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,” said Siefker-Radtke. “My hope is we will be able to add this to our treatment strategy, and 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.”

Loriot Y, Necchi A, Park SH, et al. Erdafitinib in locally advanced or metastatic urothelial carcinoma. N Engl J Med. 2019;381(4):338-348. doi: 10.1056/NEJMoa1817323.