Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) with disease recurrence after bacillus Calmette-Guérin (BCG) treatment and who are ineligible for/refuse radical cystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, a selective pan-FGFR tyrosine kinase inhibitor, versus intravesical chemotherapy in patients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment.
Patients aged ≥18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-grade Ta/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oral erdafitinib or investigator's choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpoint was recurrence-free survival (RFS). The key secondary endpoint was safety.
Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2:1 to erdafitinib (n=49) and chemotherapy (n=24). Median follow-up for RFS was 13.4 months for both groups. Median RFS was not reached for erdafitinib (95% confidence interval [CI] 16.9-not estimable) and was 11.6 months (95% CI 6.4-20.1) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6; nominal P value=0.0008). In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy.
Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, high-risk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for radical cystectomy. (Funded by Janssen Research & Development; ClinicalTrials.gov number, NCT04172675).
Annals of oncology : official journal of the European Society for Medical Oncology. 2023 Oct 05 [Epub ahead of print]
J W F Catto, B Tran, M Rouprêt, J E Gschwend, Y Loriot, H Nishiyama, J P Redorta, S Daneshmand, S A Hussain, H J Cutuli, G Procopio, V Guadalupi, N Vasdev, V Naini, L Crow, S Triantos, M Baig, G Steinberg, THOR-2 Cohort 1 Investigators
Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK; Sheffield Teaching Hospitals NHS Trust, Sheffield, UK. Electronic address: ., Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia., Department of Urology, GRC 5 Predictive Onco-Uro, Hôpital Pitié-Salpêtrière, Sorbonne University, Paris, France., Department of Urology, School of Medicine and Health, Technical University of Munich, Munich, Germany., Department of Cancer Medicine, INSERM U981, Gustave Roussy, Université Paris-Saclay, Villejuif, France., Department of Urology, Institute of Medicine, University of Tsukuba, Tsukuba, Japan., Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain., Department of Urology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA., Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK; Sheffield Teaching Hospitals NHS Trust, Sheffield, UK., Uro-oncology and Research Unit, Sirio Libanes Hospital, Buenos Aires, Argentina., Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale Tumori Milano, Milan, Italy., Hertfordshire and Bedfordshire Urological Cancer Centre, Lister Hospital, East and North Herts NHS Trust, Stevenage, UK; School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK., Janssen Research & Development, San Diego, CA, USA., Janssen Research & Development, Spring House, PA, USA., Department of Urology, Rush University Medical Center, Chicago, IL, USA.