Erdafitinib in BCG-treated high risk non-muscle invasive bladder cancer

James W.F.  Catto; Ben Tran; Morgan Roupret; Juergen E.  Gschwend; Yohann Loriot; Hiroyuki  Nishiyama; Joan P. Redorta; Siamak Daneshmand; Syed A. Hussain; Hernan J  Cutuli; Giuseppe Procopio; Valentina  Guadalupi; Nikhil Vasdev; Vahid Naini; Lauren Crow; Spyros Triantos; Mahadi Baig; Gary D. Steinberg

doi:https://doi.org/10.1016/j.annonc.2023.09.3116

Erdafitinib in BCG-treated high risk non-muscle invasive bladder cancer

James W.F. Catto, Ben Tran, Morgan Roupret, Juergen E. Gschwend, Yohann Loriot, Hiroyuki Nishiyama, Joan P. Redorta, Siamak Daneshmand, Syed A. Hussain, Hernan J Cutuli, Giuseppe Procopio, Valentina Guadalupi, Nikhil Vasdev, Vahid Naini, Lauren Crow, Spyros Triantos, Mahadi Baig, Gary D. Steinberg

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

Abstract

Background: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC)
with disease recurrence after bacillus CalmetteeGuérin (BCG) treatment and who are ineligible for/refuse radical
cystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, a
selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy in
patients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment.
Patients and methods: Patients aged 18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-grade
Ta/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oral
erdafitinib or investigator’s choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpoint
was recurrence-free survival (RFS). The key secondary endpoint was safety.
Results: Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 to
erdafitinib (n ¼ 49) and chemotherapy (n ¼ 24). Median follow-up for RFS was 13.4 months for both groups.
Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6
months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6;
nominal P value ¼ 0.0008). In this population, safety results were generally consistent with known profiles for
erdafitinib and chemotherapy.
Conclusions: Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, highrisk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for
radical cystectomy.
Key words: erdafitinib, FGFR, intravesical chemotherapy, non-muscle-invasive bladder cancer, recurrence-free survival,
safety
INTRODUCTION
The standard of care for patients with high-risk, papillary, n

Original language	English
Journal	Annals of Oncology
Early online date	21 Oct 2023
DOIs	https://doi.org/10.1016/j.annonc.2023.09.3116
Publication status	E-pub ahead of print - 21 Oct 2023

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Catto, J. W. F., Tran, B., Roupret, M., Gschwend, J. E., Loriot, Y., Nishiyama, H., Redorta, J. P., Daneshmand, S., Hussain, S. A., Cutuli, H. J., Procopio, G., Guadalupi, V., Vasdev, N., Naini, V., Crow, L., Triantos, S., Baig, M., & Steinberg, G. D. (2023). Erdafitinib in BCG-treated high risk non-muscle invasive bladder cancer. Annals of Oncology. https://doi.org/10.1016/j.annonc.2023.09.3116

@article{679af59e855d46eda9852ad871f4bbc4,

title = "Erdafitinib in BCG-treated high risk non-muscle invasive bladder cancer",

abstract = "Background: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC)with disease recurrence after bacillus CalmetteeGu{\'e}rin (BCG) treatment and who are ineligible for/refuse radicalcystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, aselective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy inpatients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment.Patients and methods: Patients aged 18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-gradeTa/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oralerdafitinib or investigator{\textquoteright}s choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpointwas recurrence-free survival (RFS). The key secondary endpoint was safety.Results: Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 toerdafitinib (n ¼ 49) and chemotherapy (n ¼ 24). Median follow-up for RFS was 13.4 months for both groups.Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6;nominal P value ¼ 0.0008). In this population, safety results were generally consistent with known profiles forerdafitinib and chemotherapy.Conclusions: Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, highrisk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible forradical cystectomy.Key words: erdafitinib, FGFR, intravesical chemotherapy, non-muscle-invasive bladder cancer, recurrence-free survival,safetyINTRODUCTIONThe standard of care for patients with high-risk, papillary, n",

author = "Catto, {James W.F.} and Ben Tran and Morgan Roupret and Gschwend, {Juergen E.} and Yohann Loriot and Hiroyuki Nishiyama and Redorta, {Joan P.} and Siamak Daneshmand and Hussain, {Syed A.} and Cutuli, {Hernan J} and Giuseppe Procopio and Valentina Guadalupi and Nikhil Vasdev and Vahid Naini and Lauren Crow and Spyros Triantos and Mahadi Baig and Steinberg, {Gary D.}",

year = "2023",

month = oct,

day = "21",

doi = "https://doi.org/10.1016/j.annonc.2023.09.3116",

language = "English",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Oxford University Press (OUP)",

}

TY - JOUR

T1 - Erdafitinib in BCG-treated high risk non-muscle invasive bladder cancer

AU - Catto, James W.F.

AU - Tran, Ben

AU - Roupret, Morgan

AU - Gschwend, Juergen E.

AU - Loriot, Yohann

AU - Nishiyama, Hiroyuki

AU - Redorta, Joan P.

AU - Daneshmand, Siamak

AU - Hussain, Syed A.

AU - Cutuli, Hernan J

AU - Procopio, Giuseppe

AU - Guadalupi, Valentina

AU - Vasdev, Nikhil

AU - Naini, Vahid

AU - Crow, Lauren

AU - Triantos, Spyros

AU - Baig, Mahadi

AU - Steinberg, Gary D.

PY - 2023/10/21

Y1 - 2023/10/21

N2 - Background: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC)with disease recurrence after bacillus CalmetteeGuérin (BCG) treatment and who are ineligible for/refuse radicalcystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, aselective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy inpatients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment.Patients and methods: Patients aged 18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-gradeTa/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oralerdafitinib or investigator’s choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpointwas recurrence-free survival (RFS). The key secondary endpoint was safety.Results: Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 toerdafitinib (n ¼ 49) and chemotherapy (n ¼ 24). Median follow-up for RFS was 13.4 months for both groups.Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6;nominal P value ¼ 0.0008). In this population, safety results were generally consistent with known profiles forerdafitinib and chemotherapy.Conclusions: Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, highrisk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible forradical cystectomy.Key words: erdafitinib, FGFR, intravesical chemotherapy, non-muscle-invasive bladder cancer, recurrence-free survival,safetyINTRODUCTIONThe standard of care for patients with high-risk, papillary, n

AB - Background: Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC)with disease recurrence after bacillus CalmetteeGuérin (BCG) treatment and who are ineligible for/refuse radicalcystectomy. FGFR alterations are commonly detected in NMIBC. We evaluated the activity of oral erdafitinib, aselective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, versus intravesical chemotherapy inpatients with high-risk NMIBC and select FGFR3/2 alterations following recurrence after BCG treatment.Patients and methods: Patients aged 18 years with recurrent, BCG-treated, papillary-only high-risk NMIBC (high-gradeTa/T1) and select FGFR alterations refusing or ineligible for radical cystectomy were randomized to 6 mg daily oralerdafitinib or investigator’s choice of intravesical chemotherapy (mitomycin C or gemcitabine). The primary endpointwas recurrence-free survival (RFS). The key secondary endpoint was safety.Results: Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 toerdafitinib (n ¼ 49) and chemotherapy (n ¼ 24). Median follow-up for RFS was 13.4 months for both groups.Median RFS was not reached for erdafitinib [95% confidence interval (CI) 16.9 months-not estimable] and was 11.6months (95% CI 6.4-20.1 months) for chemotherapy, with an estimated hazard ratio of 0.28 (95% CI 0.1-0.6;nominal P value ¼ 0.0008). In this population, safety results were generally consistent with known profiles forerdafitinib and chemotherapy.Conclusions: Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, highrisk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible forradical cystectomy.Key words: erdafitinib, FGFR, intravesical chemotherapy, non-muscle-invasive bladder cancer, recurrence-free survival,safetyINTRODUCTIONThe standard of care for patients with high-risk, papillary, n

U2 - https://doi.org/10.1016/j.annonc.2023.09.3116

DO - https://doi.org/10.1016/j.annonc.2023.09.3116

M3 - Article

SN - 0923-7534

JO - Annals of Oncology

JF - Annals of Oncology

ER -

Erdafitinib in BCG-treated high risk non-muscle invasive bladder cancer

Abstract

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