Management of Fibroblast Growth Factor Inhibitor Treatment–emergent Adverse Events of Interest in Patients with Locally Advanced or Metastatic Urothelial Carcinoma

Arlene O. Siefker-Radtke, Andrea Necchi, Se Hoon Park, Jesús García-Donas, Robert A. Huddart, Earle F. Burgess, Mark T. Fleming, Arash Rezazadeh Kalebasty, Begoña Mellado, Sergei Varlamov, Monika Joshi, Ignacio Duran, Scott T. Tagawa, Yousef Zakharia, Keqin Qi, Sydney Akapame, Spyros Triantos, Anne O'Hagan, Yohann Loriot

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2 Scopus citations


Background: Erdafitinib is indicated for the treatment of adults with locally advanced/metastatic urothelial carcinoma and susceptible FGFR3/2 alterations progressing on/after one or more lines of prior platinum-based chemotherapy. Objective: To better understand the frequency and management of select treatment-emergent adverse events (TEAEs) to enable optimal fibroblast growth factor receptor inhibitor (FGFRi) treatment. Design, setting, and participants: Longer-term efficacy and safety results of the BLC2001 (NCT02365597) trial in patients with locally advanced and unresectable or metastatic urothelial carcinoma were studied. Intervention: Erdafitinib schedule of 8 mg/d continuous in 28-d cycles, with uptitration to 9 mg/d if serum phosphate level was <5.5 mg/dl and no significant TEAEs occurred. Outcome measurements and statistical analysis: Adverse events were graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The Kaplan-Meier methodology was used for the cumulative incidence of the first onset of TEAEs by grade. Time to resolution of TEAEs was summarized descriptively. Results and limitations: At data cutoff, the median treatment duration was 5.4 mo among 101 patients receiving erdafitinib. Select TEAEs (total; grade 3) were hyperphosphatemia (78%; 2.0%), stomatitis (59%; 14%), nail events (59%; 15%), non–central serous retinopathy (non-CSR) eye disorders (56%; 5.0%), skin events (55%; 7.9%), diarrhea (55%; 4.0%), and CSR (27%; 4.0%). Select TEAEs were mostly of grade 1 or 2, and were managed effectively with dose modifications, including dose reductions or interruptions, and/or supportive concomitant therapies, resulting in few events leading to treatment discontinuation. Further work is needed to determine whether management is generalizable to the nonprotocol/general population. Conclusions: Identification of select TEAEs and appropriate management with dose modification and/or concomitant therapies resulted in improvement or resolution of most TEAEs in patients, allowing for continuation of FGFRi treatment to ensure maximum benefit. Patient summary: Early identification and proactive management are warranted to mitigate or possibly prevent erdafitinib side effects to allow for maximum drug benefit in patients with locally advanced or metastatic bladder cancer.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalEuropean Urology Open Science
StatePublished - Apr 2023

All Science Journal Classification (ASJC) codes

  • Urology

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