TY - JOUR
T1 - Infigratinib in Early-Line and Salvage Therapy for FGFR3-Altered Metastatic Urothelial Carcinoma
AU - Lyou, Yung
AU - Rosenberg, Jonathan E.
AU - Hoffman-Censits, Jean
AU - Quinn, David I.
AU - Petrylak, Daniel
AU - Galsky, Matthew
AU - Vaishampayan, Ulka
AU - De Giorgi, Ugo
AU - Gupta, Sumati
AU - Burris, Howard
AU - Rearden, Jessica
AU - Li, Ai
AU - Xu, Cindy
AU - Andresen, Corina
AU - Moran, Susan
AU - Daneshmand, Siamak
AU - Bajorin, Dean
AU - Pal, Sumanta K.
AU - Grivas, Petros
N1 - Funding Information:
Y. Lyou has received support for the present manuscript from QED Therapeutics, Inc.; grants or contracts from the American Cancer Society (Internal pilot award); and consulting fees from Pfizer and Seattle Genetics.
Funding Information:
This work was supported by QED Therapeutics Inc. , an affiliate of BridgeBio. The funder compiled and analyzed the data in collaboration with the lead authors, and interpreted data in collaboration with all authors. Editorial support was provided by Miller Medical Communications which was funded by QED Therapeutics Inc. and Helsinn Healthcare SA. All authors reviewed and critically revised the manuscript and approved the final submitted version. The corresponding author had final responsibility for the decision to submit for publication.
Publisher Copyright:
© 2021
PY - 2022/2
Y1 - 2022/2
N2 - Introduction: 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). Patients and Methods: 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. Results: 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. Conclusion: Infigratinib has notable activity in patients with mUC regardless of LOT. The findings support the evaluation of infigratinib across different settings in mUC.
AB - Introduction: 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). Patients and Methods: 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. Results: 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. Conclusion: Infigratinib has notable activity in patients with mUC regardless of LOT. The findings support the evaluation of infigratinib across different settings in mUC.
KW - Bladder cancer
KW - Efficacy
KW - FGFR inhibitors
KW - Line of therapy
KW - Safety
UR - http://www.scopus.com/inward/record.url?scp=85119056658&partnerID=8YFLogxK
U2 - 10.1016/j.clgc.2021.10.004
DO - 10.1016/j.clgc.2021.10.004
M3 - Article
C2 - 34782263
AN - SCOPUS:85119056658
SN - 1558-7673
VL - 20
SP - 35
EP - 42
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 1
ER -