Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
/ administration & dosage
Humans
Kaplan-Meier Estimate
Middle Aged
Mutation
Neoplasm Metastasis
/ drug therapy
Progression-Free Survival
Protein Kinase Inhibitors
/ administration & dosage
Protein-Tyrosine Kinases
/ antagonists & inhibitors
Pyrazoles
/ administration & dosage
Quinoxalines
/ administration & dosage
Receptors, Fibroblast Growth Factor
/ antagonists & inhibitors
Treatment Outcome
Urologic Neoplasms
/ drug therapy
Urothelium
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
25 07 2019
25 07 2019
Historique:
entrez:
25
7
2019
pubmed:
25
7
2019
medline:
2
8
2019
Statut:
ppublish
Résumé
Alterations in the gene encoding fibroblast growth factor receptor ( In this open-label, phase 2 study, we enrolled patients who had locally advanced and unresectable or metastatic urothelial carcinoma with prespecified 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
Sections du résumé
BACKGROUND
Alterations in the gene encoding fibroblast growth factor receptor (
METHODS
In this open-label, phase 2 study, we enrolled patients who had locally advanced and unresectable or metastatic urothelial carcinoma with prespecified
RESULTS
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.
CONCLUSIONS
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
Identifiants
pubmed: 31340094
doi: 10.1056/NEJMoa1817323
doi:
Substances chimiques
Antineoplastic Agents
0
Protein Kinase Inhibitors
0
Pyrazoles
0
Quinoxalines
0
Receptors, Fibroblast Growth Factor
0
erdafitinib
890E37NHMV
Protein-Tyrosine Kinases
EC 2.7.10.1
Banques de données
ClinicalTrials.gov
['NCT02365597']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
338-348Investigateurs
Wolfgang Loidl
(W)
Johannes Meran
(J)
Shahrokh Shariat
(S)
Herbert Stöger
(H)
Karel Decaestecker
(K)
Luc Dirix
(L)
Jean Pascal Machiels
(JP)
Peter Schatteman
(P)
Vincent Verschaeve
(V)
Delphine Borchiellini
(D)
Stephane Culine
(S)
Remy Delva
(R)
Aude Flechon
(A)
Marine Gross Goupil
(M)
Nadine Houédé
(N)
Florence Joly
(F)
Yohann Loriot
(Y)
Frederic Rolland
(F)
Christine Théodore
(C)
Yann Vano
(Y)
Sylvie Zanetta
(S)
Martin Bögemann
(M)
Peter Goebell
(P)
Boris Hadaschik
(B)
Florian Imkamp
(F)
Theodor Klotz
(T)
Susanne Krege
(S)
Dimitrios Manos
(D)
Matthias May
(M)
Margitta Retz
(M)
Wolfgang Schultze-Seemann
(W)
Arne Strauss
(A)
Christian Wülfing
(C)
Uwe Zimmermann
(U)
Eliahu Gez
(E)
Daniel Keizman
(D)
Avivit Peer
(A)
Eli Rosenbaum
(E)
Keren Rouvinov
(K)
Avishai Sella
(A)
Mario Airoldi
(M)
Carlo Barone
(C)
Umberto Basso
(U)
Rossana Berardi
(R)
Sergio Bracarda
(S)
Enrico Cortesi
(E)
Ugo De Giorgi
(U)
Gaetano Facchini
(G)
Luca Galli
(L)
Donatello Gasparro
(D)
Alessandra Mosca
(A)
Andrea Necchi
(A)
Armando Santoro
(A)
Giorgio Scagliotti
(G)
Cora Nanette Sternberg
(CN)
Hyo Jin Lee
(HJ)
Jae-Lyun Lee
(JL)
Se Hoon Park
(SH)
Sun Young Rha
(SY)
Ho Kyung Seo
(HK)
Dong Bok Shin
(DB)
Iurie Bulat
(I)
Cristina Cebotaru
(C)
Viorel Jinga
(V)
Dan Lungulescu
(D)
Mihai Marinca
(M)
Boris Alexeev
(B)
Adel Izmailov
(A)
Denis Khvorostenko
(D)
Eugeniy Kopyltsov
(E)
Vsevolod Matveev
(V)
Mikhail Shkolnik
(M)
Sergey Varlamov
(S)
Vladimir Vladimirov
(V)
José Ángel Arranz
(JÁ)
Joan Carles
(J)
Ignacio Duran
(I)
Albert Font
(A)
Jesus Garcia-Donas
(J)
Begoña Mellado
(B)
Victor Moreno
(V)
Jose Luis Perez Gracia
(JL)
Alvaro Pinto
(A)
Maribel Saez
(M)
Chia Chi Lin
(CC)
Yen Chuan Ou
(YC)
See Tong Pang
(ST)
Wen Pin Su
(WP)
Stephanie Gibbs
(S)
Robert Huddart
(R)
Syed Hussain
(S)
Patrick Niblock
(P)
Omi Parikh
(O)
Sarah Pascoe
(S)
Naveed Sarwar
(N)
Earle Burgess
(E)
John Burke
(J)
Karim Chamie
(K)
Nancy Dawson
(N)
Gurjyot Doshi
(G)
Mark Fleming
(M)
John Hainsworth
(J)
Sharad Jain
(S)
Monika Joshi
(M)
Tim Larson
(T)
Kristi McIntyre
(K)
Peter O'Donnell
(P)
Chong-Xian Pan
(CX)
Rahul Parikh
(R)
Arash Rezazadeh
(A)
Alison Savage
(A)
Ian Schnadig
(I)
Neal Shore
(N)
Arlene Siefker-Radtke
(A)
Sandy Srinivas
(S)
Scott Tagawa
(S)
Nicholas Vogelzang
(N)
Yousef Zakharia
(Y)
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Informations de copyright
Copyright © 2019 Massachusetts Medical Society.