Infigratinib in Early-Line and Salvage Therapy for FGFR3-Altered Metastatic Urothelial Carcinoma.
Bladder cancer
Efficacy
FGFR inhibitors
Line of therapy
Safety
Journal
Clinical genitourinary cancer
ISSN: 1938-0682
Titre abrégé: Clin Genitourin Cancer
Pays: United States
ID NLM: 101260955
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
01
09
2021
revised:
06
10
2021
accepted:
08
10
2021
pubmed:
17
11
2021
medline:
30
4
2022
entrez:
16
11
2021
Statut:
ppublish
Résumé
To describe the efficacy of infigratinib, a potent, selective fibroblast growth factor receptor (FGFR) 1-3 tyrosine kinase inhibitor, across lines of therapy (LOT) in patients with metastatic urothelial cancer (mUC). Eligible patients had mUC and prior platinum-based chemotherapy, unless contraindicated, and activating FGFR3 mutation/fusion. Patients received infigratinib 125 mg orally daily (3 weeks on/1 week off) in a single-arm, open-label study. Primary endpoint: investigator-assessed confirmed objective response rate (ORR). Disease control rate (DCR), progression-free survival (PFS), best overall response (BOR) that included unconfirmed responses, and overall survival (OS) were also assessed. Subgroup analysis of efficacy and safety outcomes by LOT was performed. Sixty-seven patients were enrolled; 13 (19.4%) received infigratinib as early-line therapy for mUC due to ineligibility to receive platinum-based chemotherapy. Overall, ORR was 25.4% (95% CI 15.5-37.5) and DCR was 64.2% (95% CI 51.5-75.5). ORR was 30.8% (95% CI 9.1-61.4) with early-line infigratinib and 24.1% (95% CI 13.5-37.6) for ≥2 LOT. DCR was 46.2% (95% CI 19.2-74.9) for early-line and 68.5% (95% CI 54.4-80.5) for ≥2 LOT. PFS and OS appeared similar in both groups. Thirteen of 59 patients with a bladder primary tumor received early-line treatment with an ORR of 30.5% (95% CI 9.1-61.4), and 46 received ≥2 LOT with an ORR of 20.3% (95% CI 9.4-33.9); BOR was 38.5% (95% CI: 13.9-68.4%) and 42.6% (95% CI: 29.2-56.8%) in the early-line and salvage settings, respectively. Eight patients with upper tract urothelial carcinoma received salvage therapy (ORR, 50.0%; DCR, 100.0%). No significant differences in toxicities between LOT were observed. Infigratinib has notable activity in patients with mUC regardless of LOT. The findings support the evaluation of infigratinib across different settings in mUC.
Identifiants
pubmed: 34782263
pii: S1558-7673(21)00195-6
doi: 10.1016/j.clgc.2021.10.004
pmc: PMC9460895
mid: NIHMS1826959
pii:
doi:
Substances chimiques
Phenylurea Compounds
0
Pyrimidines
0
Platinum
49DFR088MY
infigratinib
A4055ME1VK
FGFR3 protein, human
EC 2.7.10.1
Receptor, Fibroblast Growth Factor, Type 3
EC 2.7.10.1
Types de publication
Clinical Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
35-42Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
Copyright © 2021. Published by Elsevier Inc.
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