Erdafitinib efficacy in bladder cancer sustained with long-term follow-up

Long-term follow-up from the pivotal phase 2 BLC2001 study showed continued efficacy with the pan-FGFR inhibitor erdafitinib (Balversa) in patients with locally advanced or metastatic urothelial carcinoma, according to findings published in The Lancet Oncology.1

At a median follow-up of 24 months, the objective response rate with erdafitinib was 40%, comprising a complete response rate of 4.0% and a partial response rate of 36.0%. No new safety signals emerged with the extended follow-up compared with the safety data from the primary analysis.

“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,” lead study author Arlene O. Siefker-Radtke, MD, a professor in the Department of Genitourinary Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, and coauthors wrote in their study conclusion.

Based on the primary findings from BLC2001, the FDA granted an accelerated approval to 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 updated results for the open-label, single-arm, multicenter BLC2001 trial (NCT02365597) included data for 101 evaluable 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).

The median patient age was 67 years (range, 61-73). Ninety-three percent of patients had an ECOG performance status of 0 or 1 and 77% had visceral metastases. Only 10 patients had not received prior therapy. The remaining patients had received 1 (n = 48), 2 (n = 28) or ≥3 (n = 15) lines of therapy. Twelve percent of patients were chemotherapy-naïve, with 88% having progressed or relapsed after receiving chemotherapy. Twenty-four percent of patient had prior 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 median duration of response was 6.0 months (95% CI, 4.2-7.5). Thirty-one (31%) of the 101 patients reached a response that lasted for at least 1 year. Beyond the 40 patients (40%) with a response, an additional 41 of the 101 patients had stable disease, translating to an overall disease control rate of 80%.

All-cause grade 3/4 treatment emergent adverse events (TEAEs) occurred in 71% of the 101 evaluable patients. The most frequently reported all-cause grade 3/4 TEAEs were stomatitis (14%) and hyponatremia (11%). No treatment-related deaths occurred.

Summarizing the implications of these long-term findings, Siefker-Radtke et al wrote, “The long-term follow-up of this study confirms the benefit of erdafitinib, an FGFR inhibitor, for the treatment of patients with locally advanced or metastatic urothelial cancer and specific

FGFR alterations. Further research, in a randomized, controlled, phase 3 study in patients with advanced urothelial cancer, is ongoing to evaluate erdafitinib as second-line monotherapy compared with a PD-1 inhibitor or chemotherapy. Another study is ongoing to evaluate erdafitinib in combination with a PD-1 inhibitor (cetrelimab) in first-line treatment of patients with metastatic urothelial carcinoma who are ineligible for cisplatin.”


1. Siefker-Radtke AO, Necchi A, Park SH, et al. Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study [published online January 11, 2022]. Lancet Oncol. doi: 10.1016/S1470-2045(21)00660-4