Infigratinib in Early-Line and Salvage Therapy for FGFR3-Altered Metastatic Urothelial Carcinoma

Yung Lyou; Jonathan E. Rosenberg; Jean Hoffman-Censits; David I. Quinn; Daniel Petrylak; Matthew Galsky; Ulka Vaishampayan; Ugo De Giorgi; Sumati Gupta; Howard Burris; Jessica Rearden; Ai Li; Cindy Xu; Corina Andresen; Susan Moran; Siamak Daneshmand; Dean Bajorin; Sumanta K. Pal; Petros Grivas

doi:10.1016/j.clgc.2021.10.004

Infigratinib in Early-Line and Salvage Therapy for FGFR3-Altered Metastatic Urothelial Carcinoma

Yung Lyou, Jonathan E. Rosenberg, Jean Hoffman-Censits, David I. Quinn, Daniel Petrylak, Matthew Galsky, Ulka Vaishampayan, Ugo De Giorgi, Sumati Gupta, Howard Burris, Jessica Rearden, Ai Li, Cindy Xu, Corina Andresen, Susan Moran, Siamak Daneshmand, Dean Bajorin, Sumanta K. Pal, Petros Grivas

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Pages (from-to)	35-42
Number of pages	8
Journal	Clinical Genitourinary Cancer
Volume	20
Issue number	1
DOIs	https://doi.org/10.1016/j.clgc.2021.10.004
State	Published - Feb 2022

Keywords

Bladder cancer
Efficacy
FGFR inhibitors
Line of therapy
Safety

ASJC Scopus subject areas

Urology
Oncology

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10.1016/j.clgc.2021.10.004

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Lyou, Y., Rosenberg, J. E., Hoffman-Censits, J., Quinn, D. I., Petrylak, D., Galsky, M., Vaishampayan, U., De Giorgi, U., Gupta, S., Burris, H., Rearden, J., Li, A., Xu, C., Andresen, C., Moran, S., Daneshmand, S., Bajorin, D., Pal, S. K., & Grivas, P. (2022). Infigratinib in Early-Line and Salvage Therapy for FGFR3-Altered Metastatic Urothelial Carcinoma. Clinical Genitourinary Cancer, 20(1), 35-42. https://doi.org/10.1016/j.clgc.2021.10.004

Lyou, Y, Rosenberg, JE, Hoffman-Censits, J, Quinn, DI, Petrylak, D, Galsky, M, Vaishampayan, U, De Giorgi, U, Gupta, S, Burris, H, Rearden, J, Li, A, Xu, C, Andresen, C, Moran, S, Daneshmand, S, Bajorin, D, Pal, SK & Grivas, P 2022, 'Infigratinib in Early-Line and Salvage Therapy for FGFR3-Altered Metastatic Urothelial Carcinoma', Clinical Genitourinary Cancer, vol. 20, no. 1, pp. 35-42. https://doi.org/10.1016/j.clgc.2021.10.004

@article{22d3f0e2b540466e996f87daaf281ebe,

title = "Infigratinib in Early-Line and Salvage Therapy for FGFR3-Altered Metastatic Urothelial Carcinoma",

abstract = "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.",

keywords = "Bladder cancer, Efficacy, FGFR inhibitors, Line of therapy, Safety",

author = "Yung Lyou and Rosenberg, {Jonathan E.} and Jean Hoffman-Censits and Quinn, {David I.} and Daniel Petrylak and Matthew Galsky and Ulka Vaishampayan and {De Giorgi}, Ugo and Sumati Gupta and Howard Burris and Jessica Rearden and Ai Li and Cindy Xu and Corina Andresen and Susan Moran and Siamak Daneshmand and Dean Bajorin and Pal, {Sumanta K.} and Petros Grivas",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2022",

month = feb,

doi = "10.1016/j.clgc.2021.10.004",

language = "English (US)",

volume = "20",

pages = "35--42",

journal = "Clinical Genitourinary Cancer",

issn = "1558-7673",

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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

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

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DO - 10.1016/j.clgc.2021.10.004

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Infigratinib in Early-Line and Salvage Therapy for FGFR3-Altered Metastatic Urothelial Carcinoma

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