Erdafitinib for Patients With Advanced Urothelial Carcinoma and FGFR Alterations

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As reported in The Lancet Oncology by Arlene O. Siefker-Radtke, MD, and colleagues, the final analysis of the phase II BLC2001 trial has shown maintained activity of the pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor erdafitinib in patients with locally advanced unresectable or metastatic urothelial carcinoma with FGFR alterations.

Previously, erdafitinib showed activity in the primary analysis, which was performed at a median follow-up of 11 months.

Arlene O. Siefker-Radtke, MD

Arlene O. Siefker-Radtke, MD

Study Details

The study enrolled patients from sites in 14 countries between May 2015 and 2018. Patients had to have at least one prespecified FGFR alteration, as well as progressive disease after at least one systemic course of chemotherapy or within 12 months of neoadjuvant or adjuvant chemotherapy (or had to be ineligible to receive cisplatin). A total of 101 patients received the selected regimen of 8 mg of oral erdafitinib once daily continuously in 28-day cycles, with provision for pharmacodynamically guided up-titration to 9 mg/d (8 mg/d UpT regimen).

Overall, 69% of patients had FGFR mutations, 25% had fusions, and 6% had both. The most common mutation was FGFR3S249C (46%). The primary endpoint was investigator-assessed objective response rate.


Among the 101 patients, 60 received 8 mg/d and 41 were up-titrated to 9 mg/d. Median follow-up for efficacy for the final analysis at data cutoff (August 2019) was 24.0 months (interquartile range = 22.7–26.6 months).

Objective response was observed in 40 patients (40%, 95% confidence interval [CI] = 30%–49%), with complete response in 4 (4%). An additional 41 patients (41%) had stable disease for longer than 36 days, yielding a disease control rate of 80% (95% CI = 72%–88%). Median duration of response was 6.0 months (95% CI = 4.2–7.5 months).

Median progression-free survival was 5.5 months (95% CI = 4.3–6.0 months), with a 12-month rate of 21% (95% CI = 13%–29%). Median overall survival was 11.3 months (95% CI = 9.7–15.2 months), with 12- and 24-month rates of 49% (95% CI = 39%–59%) and 31% (95% CI = 22%–40%).


  • Objective response was observed in 40% of patients.
  • The disease control rate was 80%.

Adverse Events

The safety profile was similar to that reported in the primary analysis; no new safety signals were detected during the longer follow-up. The most common adverse events of any grade were hyperphosphatemia (78%), diarrhea (54%), dry mouth (46%), and decreased appetite (41%).  Grade 3 or 4 adverse events occurred in 71% of patients, most commonly stomatitis (14%), hyponatremia (11%), and asthenia (8%). Central serous retinopathy of any grade occurred in 27 patients (27%, grade 3 in 4 patients).

Serious adverse events occurred in 45% of patients; most commonly, urinary tract infection (4%), general physical health deterioration (3%), and hematuria (3%). Treatment-related adverse events led to discontinuation of treatment in 16% of patients. No treatment-related deaths were reported.  

The investigators concluded, “With longer follow-up, treatment with the selected regimen of erdafitinib showed consistent activity and a manageable safety profile in patients with locally advanced or metastatic urothelial carcinoma and prespecified FGFR alterations.”

Dr. Siefker-Radtke, of the Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Janssen Research & Development. For full disclosures of the study authors, visit

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