Journal article
Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma
The New England journal of medicine, Vol.381(4), pp.338-348
07/25/2019
DOI: 10.1056/NEJMoa1817323
PMID: 31340094
Abstract
Alterations in the gene encoding fibroblast growth factor receptor (
) 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
alterations.
In this open-label, phase 2 study, we enrolled patients who had locally advanced and unresectable or metastatic urothelial carcinoma with prespecified
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.
A total of 99 patients in the selected-regimen group received a median of five cycles of erdafitinib. Of these patients, 43% had received at least two previous courses of treatment, 79% had visceral metastases, and 53% had a creatinine clearance of less than 60 ml per minute. The rate of confirmed response to erdafitinib therapy was 40% (3% with a complete response and 37% with a partial response). Among the 22 patients who had undergone previous immunotherapy, the confirmed response rate was 59%. The median duration of progression-free survival was 5.5 months, and the median duration of overall survival was 13.8 months. Treatment-related adverse events of grade 3 or higher, which were managed mainly by dose adjustments, were reported in 46% of the patients; 13% of the patients discontinued treatment because of adverse events. There were no treatment-related deaths.
The use of erdafitinib was associated with an objective tumor response in 40% of previously treated patients who had locally advanced and unresectable or metastatic urothelial carcinoma with
alterations. Treatment-related grade 3 or higher adverse events were reported in nearly half the patients. (Funded by Janssen Research and Development; BLC2001 ClinicalTrials.gov number, NCT02365597.).
Details
- Title: Subtitle
- Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma
- Creators
- Yohann Loriot - InsermAndrea Necchi - Fondazione IRCCS Istituto Nazionale dei TumoriSe Hoon Park - Samsung Medical CenterJesus Garcia-Donas - Centro Oncológico de GaliciaRobert Huddart - Institute of Cancer ResearchEarle Burgess - Levine Cancer InstituteMark Fleming - Virginia Oncology AssociatesArash Rezazadeh - Norton HealthcareBegoña Mellado - Universitat de BarcelonaSergey VarlamovMonika Joshi - Penn State Milton S. Hershey Medical CenterIgnacio Duran - Marqués de Valdecilla University HospitalScott T Tagawa - Cornell UniversityYousef Zakharia - University of IowaBob Zhong - JanssenKim Stuyckens - JanssenAdemi Santiago-Walker - JanssenPeter De Porre - JanssenAnne O'HaganAnjali Avadhani - JanssenArlene O Siefker-Radtke - The University of Texas MD Anderson Cancer CenterBLC2001 Study Group
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.381(4), pp.338-348
- DOI
- 10.1056/NEJMoa1817323
- PMID
- 31340094
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Language
- English
- Date published
- 07/25/2019
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984548265502771
Metrics
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