European Urology Open Science (Apr 2023)

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

Journal volume & issue
Vol. 50
pp. 1 – 9

Abstract

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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.

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