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Multicenter Study
. 2025 Nov 11;30(11):oyaf342.
doi: 10.1093/oncolo/oyaf342.

Efficacy of erdafitinib before or after enfortumab vedotin in FGFR3-altered advanced urothelial cancer: analysis of the UNITE collaborative study

Cindy Y Jiang  1 , Hyunsoo Hwang  2 , Ilana Y Epstein  3 , Dimitra Rafailia Bakaloudi  4 , Rafee Talukder  5 , Amy K Taylor  6 , Amanda Nizam  7 , Tanya Jindal  8 , Michael J Glover  9 , Ali Raza Khaki  9 , Pedro C Barata  10 , Charles B Nguyen  11 , Eugene Oh  12 , Nancy B Davis  13 , Hannah Mabey  14 , Christopher J Hoimes  15 , Sean T Evans  16 , Bashar Abuqayas  17 , Emily Lemke  18 , Irene Tsung  12 , Wei Qiao  1 , Deepak Kilari  18 , Yousef Zakharia  17 , Mehmet A Bilen  16 , Matthew I Milowsky  14 , Sumit A Shah  9 , Shilpa Gupta  7 , Hamid Emamekhoo  6 , Joaquim Bellmunt  3 , Ajjai S Alva  12 , Petros Grivas  4 , Pavlos Msaouel  1 , Vadim S Koshkin  8 , Matthew T Campbell  1 , Omar Alhalabi  1
Affiliations
Multicenter Study

Efficacy of erdafitinib before or after enfortumab vedotin in FGFR3-altered advanced urothelial cancer: analysis of the UNITE collaborative study

Cindy Y Jiang et al. Oncologist. .

Abstract

Background: Erdafitinib is approved for locally advanced/metastatic urothelial cancer (LA/mUC). As enfortumab vedotin (EV) plus pembrolizumab enters frontline management, outcomes with erdafitinib pre- and post-EV are clinically relevant but not specifically evaluated in clinical trials.

Methods: UNITE is a multi-institutional retrospective study of patients with LA/mUC treated with novel targeted agents. All patients with FGFR3 alterations treated with EV only, erdafitinib then EV (Erda->EV), and EV then erdafitinib (EV->Erda) were included. Sequential treatment with EV and Erda was not required. Primary endpoints were observed response rates (ORR) and progression-free survival (PFS); secondary endpoint was overall survival (OS).

Results: We identified 83 patients with FGFR3 alterations and separated them into three cohorts: EV only (n = 44), Erda->EV (n = 24), and EV->Erda (n = 15). Most (72%) received ≥2 lines of therapy before erdafitinib (checkpoint inhibitor [87%], platinum-based chemotherapy [64%]). Median PFS with erdafitinib for EV-naïve cohort was 7.5 months and in EV-treated cohort 4.0 months (HR 0.78; 95% CI 0.35-1.7). ORR with erdafitinib for EV-naïve was 33% and EV-treated 31% (OR 1.1; 95% CI 0.29-4.1). Median PFS with EV for patients who were erdafitinib-naïve was 6 months and in erdafitinib-treated 5.3 months (HR 0.61; 95% CI 0.34-1.09). ORR with EV was 54% in erdafitinib-naïve cohort and 32% in erdafitinib-treated cohort (OR 2.5; 95% CI 0.87-6.3).

Conclusion: In patients with FGFR3-altered LA/mUC, erdafitinib is active pre- and post-EV. Outcomes with erdafitinib were consistent with clinical trial data generated prior to broader frontline use of EV. Findings are hypothesis-generating and given small sample size should be interpreted with caution.

Keywords: FGFR3; advanced urothelial carcinoma; bladder cancer; enfortumab vedotin; erdafitinib.

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Conflict of interest statement

C.Y.J. reports no conflicts of interest. H.H. reports no conflicts of interest. I.Y.E. reports no conflicts of interest. D.R.B. reports no conflicts of interest. R.T. reports no conflicts of interest. A.K.T. reports no conflicts of interest. A.N. reports the following disclosures—Consulting or advisory role: AVEO Oncology, Astellas Pharma, Seagen, Pfizer, EMD Serono/Merck KGaA, Mashup Media; Honoraria: Cleveland Clinic, Aptitude Health, Targeted Oncology, IntegrityCE, MECC Global Meetings, ASCO, Doximity, SignifyMD; Bladder Cancer Section Editor: GU Oncology Now (part of Mashup Media); Travel and accommodation expenses: ASCO, MECC Global Meetings, Mashup Media. T.J. reports no conflicts of interest. M.J.G. reports no conflicts of interest. A.R.K. reports the following disclosures—research funding to the institution from 23andMe, Acrivon Therapeutics, Janssen, Pfizer. P.C.B. reports grants or personal fees from Astellas; AstraZeneca; Bayer; Eisai; ESSA Pharma; Ipsen; Caris Life Sciences; Exelixis; Janssen; EMD Serono; Dendreon; Pfizer, Seattle Genetics; Merck; Merus; BMS; Bayer, Guardant Health; Myovant; UroToday; OncLive; Targeted Oncology; Novartis. C.B.N. reports the following disclosures—Travel: DAVA oncology; Honoraria: MJH associates. E.O. reports no conflicts of interest. N.B.D. reports the following disclosures—currently employed by Merck & Co. H.M. reports the following disclosures—reports no conflicts of interest. P.M. reports the following disclosures—reports no conflicts of interest. C.J.H. reports the following disclosures—consulting with Seagen and Merck. S.T.E. reports no conflicts of interest. B.A. reports no conflicts of interest. E.L. reports no conflicts of interest. I.T. reports no conflicts of interest. W.Q. reports no conflicts of interest. D.K. reports the following disclosures—Consulting: Janssen, Exelixis, Foundation medicine, Eisai, Bayer, Myovant, Merck, Cardinal Health, Targeted oncology, Aptitude health Binaytara foundation. Speakers bureau: Pfizer, Eisai, Aveo Oncology, Institutional funding: Exelixis, GNE, SOBI, AstraZeneca. Y.Z. reports the following disclosures—Advisory Board: Bristol Myers Squibb, Seagen, Janssen, Eisai, Exelixis, Genzyme Corporation, AstraZeneca, Pfizer, EMD Serono, Gilead. M.A.B. reports the following disclosures—reports no conflicts of interest. M.I.M. reports the following disclosures—reports no conflicts of interest. Stock and Other Ownership Interests: Pfizer, Gilead Sciences; Research Funding (institutional): Merck, Bristol-Myers Squibb, Mirati Therapeutics, Seagen, Alliance for Foundation Trials, Alliance for Clinical Trials in Oncology, Clovis Oncology, Arvinas, ALX Oncology, Hoosier Cancer Research Network, Novartis, Acrivon Therapeutics, Astellas Pharma, Genentech, Accuray, PCCTC, G1 Therapeutics, Onco4, Flare Therapeutics, Loxo/Lilly, Roche; Other Relationship: Elsevier, Medscape, Research to Practice, Prime Education. S.A.S. reports the following disclosures—reports no conflicts of interest. S.G. reports the following disclosures—Consulting: Bristol Myers Squibb, Merck, Novartis, Johnson and Johnson, Pfizer, Foundation Medicine Research Funding: Bristol Myers Squibb, Roche, Tyra Biosciences, Merck, Novartis, Flare Therapeutics. H.E. reports the following disclosures—Consulting or advisory role for Janssen Biotech, Cardinal Health, BMS, Eisai. P.G. reports the following disclosures (last 2 years) – Consulting with MSD, Bristol Myers Squibb, AstraZeneca, EMD Serono, Pfizer, Janssen, Roche, Astellas Pharma, Gilead Sciences, Fresenius Kabi, Strata Oncology, AbbVie, Bicycle Therapeutics, Replimune, Daiichi Sankyo, Foundation Medicine, Eli Lilly, and research funding from Bristol-Myers Squibb, MSD, QED Therapeutics, EMD Serono, Gilead Sciences, Acrivon Therapeutics, ALX Oncology, Genentech (paid to their institution). J.B. reports the following disclosures—reports no conflicts of interest. A.S.A. reports the following disclosures—reports no conflicts of interest. V.S.K. reports the following disclosures—Consulting or advisory role for Astellas, Bicycle Therapeutics, BMS, Janssen, Loxo Oncology, Merck, MSD, Pfizer/Seagen, Roche/Genentech, Tempus and research funding to the institution from Astellas, Curium, Eli Lilly, Gilead, Merck, Novartis, Nektar, Seagen/Pfizer, Taiho, Tyra Biosciences. M.T.C. reports the following disclosures—receives research support from AstraZeneca, Exelixis, Janssen Pfizer, United States Department of Defense served as consultant to Eisai, Exelixis, Pfizer and SeaGen. O.A reports the following disclosures—received scientific advisory board fees from Seagen, Adaptimmune, Bicycle Therapeutics, and Silverback Therapeutics, and research funding to the institution from AstraZeneca, Ikena Oncology, Genentech, and Arcus Biosciences.

Figures

Figure 1.
Figure 1.
FGFR3 alterations based on sequence of treatment. (A) Pie chart showing breakdown of FGFR3 alterations of patients treated with erdafitinib first then EV, (B) patients treated with EV first then erdafitinib, and (C) patients who received EV only and never received erdafitinib. *3 patients had two FGFR3 alterations: S249C + FGFR3 copy number gain, FGFR3-TACC3 + FGFR3 amplification, S249C + FGFR3 amplification. **1 patient had two FGFR3 alterations: T807 + V555L. ***6 patients had two FGFR3 alterations: S249C + FGFR3 Amplification, E42A + S108R, S249C + FGFR3 Amplification, S249C + R248C, FGFR3-TACC3 + FGFR3 Amplification, R246C + FGFR3 Amplification. Abbreviations: EV, enfortumab vedotin; FGFR3, fibroblast growth factor receptor 3.
Figure 2.
Figure 2.
Progression-free survival to erdafitinib and EV. (A) Progression-free survival (PFS) to erdafitinib in patients without prior exposure to EV (EV-naïve) compared to patients who previously received EV treatment (EV-treated) using Kaplan Meier (KM) method. PFS measured from start of erdafitinib. (B) PFS to EV in patients without prior exposure to erdafitinib (erda- naïve) compared to patients previously treated with erdafitinib (erda-treated). Illustrated with KM curves. PFS measured from start of EV treatment. Abbreviations: EV, enfortumab vedotin; erda, erdafitinib; HR, hazard ratio; CI, confidence interval.
Figure 3.
Figure 3.
Survival outcomes to erdafitinib and EV for all patients. (A) Overall survival (OS) and (B) progression-free survival (PFS) to erdafitinib treatment in all patients combined, regardless of prior therapy exposure (n = 39). OS and PFS were measured from initiation of erdafitinib treatment. (C) OS and (D) PFS to enfortumab vedotin (EV) in all patients combined, regardless of prior treatments received (n = 83). OS and PFS were measured from EV treatment start. Abbreviation: EV, enfortumab vedotin.
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