Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study.

Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, was shown to be clinically active and tolerable in patients with advanced urothelial carcinoma and prespecified FGFR alterations in the primary analysis of the BLC2001 study at median 11 months of follow-up. We aimed to assess the long-term efficacy and safety of the selected regimen of erdafitinib determined in the initial part of the study.

The open-label, non-comparator, phase 2, BLC2001 study was done at 126 medical centres in 14 countries across Asia, Europe, and North America. Eligible patients were aged 18 years or older with locally advanced and unresectable or metastatic urothelial carcinoma, at least one prespecified FGFR alteration, an Eastern Cooperative Oncology Group performance status of 0-2, and progressive disease after receiving at least one systemic chemotherapy or within 12 months of neoadjuvant or adjuvant chemotherapy or were ineligible for cisplatin. The selected regimen determined in the initial part of the study was continuous once daily 8 mg/day oral erdafitinib in 28-day cycles, with provision for pharmacodynamically guided uptitration to 9 mg/day (8 mg/day UpT). The primary endpoint was investigator-assessed confirmed objective response rate according to Response Evaluation Criteria In Solid Tumors version 1.1. Efficacy and safety were analysed in all treated patients who received at least one dose of erdafitinib. This is the final analysis of this study. This study is registered with ClinicalTrials.gov, NCT02365597.

Between May 25, 2015, and Aug 9, 2018, 2328 patients were screened, of whom 212 were enrolled and 101 were treated with the selected erdafitinib 8 mg/day UpT regimen. The data cutoff date for this analysis was Aug 9, 2019. Median efficacy follow-up was 24·0 months (IQR 22·7-26·6). The investigator-assessed objective response rate for patients treated with the selected erdafitinib regimen was 40 (40%; 95% CI 30-49) of 101 patients. The safety profile remained similar to that in the primary analysis, with no new safety signals reported with longer follow-up. Grade 3-4 treatment-emergent adverse events of any causality occurred in 72 (71%) of 101 patients. The most common grade 3-4 treatment-emergent adverse events of any cause were stomatitis (in 14 [14%] of 101 patients) and hyponatraemia (in 11 [11%]). There were no treatment-related deaths.

With longer follow-up, treatment with the selected regimen of erdafitinib showed consistent activity and a manageable safety profile in patients with locally advanced or metastatic urothelial carcinoma and prespecified FGFR alterations.

Janssen Research & Development.

The Lancet. Oncology. 2022 Jan 11 [Epub ahead of print]

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, Sydney Akapame, Ademi E Santiago-Walker, Manish Monga, Anne O'Hagan, Yohann Loriot, BLC2001 Study Group

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ., Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy., Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Medical Oncology Department, Fundacion Hospital de Madrid and IMMA Medicine Faculty, San Pablo CEU University, Madrid, Spain., Section of Radiotherapy and Imaging, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK., Medical Oncology Department, Levine Cancer Institute, Charlotte, NC, USA., Medical Oncology Department, Virginia Oncology Associates, US Oncology Research, Norfolk, VA, USA., Department of Medical Oncology, Norton Healthcare, Louisville, KY, USA., Medical Oncology Department, Hospital Clinic Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain., Department of Urologic Oncology, Altai Regional Cancer Center, Barnaul, Russia., Department of Medicine, Penn State Cancer Institute, Hershey, PA, USA., Department of Medical Oncology, Hospital Universitario Marqués de Valdecilla, Santander, Spain., Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, NY, USA., Department of Internal Medicine, University of Iowa, Holden Comprehensive Cancer Center, Iowa City, IA, USA., Janssen Research & Development, Spring House, PA, USA., Department of Cancer Medicine, INSERM U981, Gustave Roussy, Université Paris-Saclay, Villejuif, France.

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