Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma

Yohann Loriot (1, 2) , Andrea Necchi (3, 2) , Se Hoon Park (4, 2) , Jesus Garcia-Donas (5, 2) , Robert Huddart (6, 2) , Earle Burgess (7, 2) , Mark Fleming (8, 2) , Arash Rezazadeh (9, 2) , Begoña Mellado (10, 2) , Sergey Varlamov (11, 2) , Monika Joshi (12, 2) , Ignacio Duran (13, 2) , Scott Tagawa (14, 2) , Yousef Zakharia (15, 2) , Bob Zhong (16, 2) , Kim Stuyckens (16, 2) , Ademi Santiago-Walker (16, 2) , Peter de Porre (17, 2) , Anne O’hagan (16, 2) , Anjali Avadhani (16, 2) , Arlene Siefker-Radtke (2) , Nadine Houédé (18, 19)

1 Département de médecine oncologique [Gustave Roussy]
2 U981 - Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse
3 IRCCS Istituto Nazionale dei Tumori [Milano]
4 Samsung Medical Center Sungkyunkwan University School of Medicine
5 Centro Integral Oncologico Clara Campal
6 Academic Radiotherapy Unit
7 The Levine Cancer Institute
8 Virginia Oncology Associates
9 University of Louisville
10 Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
11 Department of Scientific Information Analyses, Siberian Research Institute of Cheese-Making, Barnaul, Russia
12 Penn State - Pennsylvania State University
13 Marqués de Valdecilla University Hospital [Santander]
14 Weill Medical College of Cornell University [New York]
15 Department of Pediatrics and Holden Comprehensive Cancer Center [Iowa City, USA]
16 Janssen Research & Development [Spring House, PA, USA]
17 Janssen Pharmaceutica [Beerse]
18 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
19 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes

Alterations in the gene encoding fibroblast growth factor receptor (FGFR) are common in urothelial carcinoma and may be associated with lower sensitivity to immune interventions. Erdafitinib, a tyrosine kinase inhibitor of FGFR1-4, has shown antitumor activity in preclinical models and in a phase 1 study involving patients with FGFR alterations. Methods: In this open-label, phase 2 study, we enrolled patients who had locally advanced and unresectable or metastatic urothelial carcinoma with prespecified FGFR alterations. All the patients had a history of disease progression during or after at least one course of chemotherapy or within 12 months after neoadjuvant or adjuvant chemotherapy. Prior immunotherapy was allowed. We initially randomly assigned the patients to receive erdafitinib in either an intermittent or a continuous regimen in the dose-selection phase of the study. On the basis of an interim analysis, the starting dose was set at 8 mg per day in a continuous regimen (selected-regimen group), with provision for a pharmacodynamically guided dose escalation to 9 mg. The primary end point was the objective response rate. Key secondary end points included progression-free survival, duration of response, and overall survival.

Domaines: Cancer; Sciences pharmaceutiques

Yohann Loriot, Andrea Necchi, Se Hoon Park, Jesus Garcia-Donas, Robert Huddart, et al.. Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. New England Journal of Medicine, 2019, 381 (4), pp.338-348. ⟨10.1056/NEJMoa1817323⟩. ⟨hal-02930806⟩