Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma

Author(s): Yohann Loriot, M.D., Ph.D., Nobuaki Matsubara, M.D., Se Hoon Park, M.D., Ph.D., Robert A. Huddart, M.B., B.S., Ph.D., Earle F. Burgess, M.D., Nadine Houede, M.D., Severine Banek, M.D., Valentina Guadalupi, M.D., Ja Hyeon Ku, M.D., Ph.D., Begoña P. Valderrama, M.D., Ben Tran, M.B., B.S., Spyros Triantos, M.D., et al., for the THOR Cohort 1 Investigators*
Source: N Engl J Med 2023; 389:1961-1971 DOI: 10.1056/NEJMoa2308849
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

Erdafatinib was compared to chemo in the >=2nd line in patients who had FGFR2/3 mutations, fusions or alterations with metastatic bladder cancer. Survival endpoints were superior in the targeted group with a overall survival of 12 vs. eight months.

In my experience, the challenge with this group of targeted agents is tolerability.


Erdafitinib is a pan–fibroblast growth factor receptor (FGFR) inhibitor approved for the treatment of locally advanced or metastatic urothelial carcinoma in adults with susceptible FGFR3/2 alterations who have progression after platinum-containing chemotherapy. The effects of erdafitinib in patients with FGFR-altered metastatic urothelial carcinoma who have progression during or after treatment with checkpoint inhibitors (anti–programmed cell death protein 1 [PD-1] or anti–programmed death ligand 1 [PD-L1] agents) are unclear.


We conducted a global phase 3 trial of erdafitinib as compared with chemotherapy in patients with metastatic urothelial carcinoma with susceptible FGFR3/2 alterations who had progression after one or two previous treatments that included an anti–PD-1 or anti–PD-L1. Patients were randomly assigned in a 1:1 ratio to receive erdafitinib or the investigator’s choice of chemotherapy (docetaxel or vinflunine). The primary end point was overall survival.


A total of 266 patients underwent randomization: 136 to the erdafitinib group and 130 to the chemotherapy group. The median follow-up was 15.9 months. The median overall survival was significantly longer with erdafitinib than with chemotherapy (12.1 months vs. 7.8 months; hazard ratio for death, 0.64; 95% confidence interval [CI], 0.47 to 0.88; P=0.005). The median progression-free survival was also longer with erdafitinib than with chemotherapy (5.6 months vs. 2.7 months; hazard ratio for progression or death, 0.58; 95% CI, 0.44 to 0.78; P<0.001). The incidence of grade 3 or 4 treatment-related adverse events was similar in the two groups (45.9% in the erdafitinib group and 46.4% in the chemotherapy group). Treatment-related adverse events that led to death were less common with erdafitinib than with chemotherapy (in 0.7% vs. 5.4% of patients).


Erdafitinib therapy resulted in significantly longer overall survival than chemotherapy among patients with metastatic urothelial carcinoma and FGFR alterations after previous anti–PD-1 or anti–PD-L1 treatment. (Funded by Janssen Research and Development; THOR number, NCT03390504. opens in new tab.)

Author Affiliations

From the Department of Cancer Medicine, INSERM Unité 981, Gustave Roussy, Université Paris-Saclay, Villejuif (Y.L.), the Department of Medical Oncology, Institut de Cancérologie du Gard, Centre Hospitalier Universitaire Caremeau, Nîmes (N.H.), and Montpellier University, Montpellier (N.H.) — all in France; the Department of Medical Oncology, National Cancer Center Hospital East, Chiba, Japan (N.M.); the Division of Hematology and Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine (S.H.P.), and Seoul National University Hospital (J.H.K.) — both in Seoul, South Korea; the Section of Radiotherapy and Imaging, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, United Kingdom (R.A.H.); Medical Oncology, Levine Cancer Institute, Atrium Health, Charlotte, NC (E.F.B.); the Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany (S.B.); the Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (V.G.); the Department of Medical Oncology, Hospital Universitario Virgen del Rocío, Seville, Spain (B.P.V.); the Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia (B.T.); Janssen Research and Development, Spring House, PA (S.T., Y.K., S.A., N.L.S.); Janssen Research and Development, Beerse, Belgium (K.D.); Janssen Research and Development, Raritan, NJ (S.M.); and the Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston (A.O.S.-R.).

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