Erdafitinib in BCG-treated high-risk non-muscle-invasive bladder cancer
James W.F. Catto, Ben Tran, Morgan Rouprêt, Juergen E. Gschwend, Yohann Loriot, Hiroyuki Nishiyama, Juan Palou Redorta, Siamak Daneshmand, Syed A. Hussain, Hernán Cutuli, Giuseppe Procopio, Valentina Guadalupi, Nikhil Vasdev, Vahid Naini, Lowell T. Crow, Spyros Triantos, Mahadi Baig, Gregory R. Steinberg, Rubén H. Bengió, Hernán Cutuli, Jorge Salinas, Filip Ameye, Steven Joniau, Diogo Augusto Rodrigues Da Rosa, Karine Martins da Trindade, Murilo Almeida Luz, Mário Henrique Bueno Bavaresco, Adriano de Paula, Jose Santiag, Shaogang Wang, Dingwei Ye, Martin Boegemann, Florian Roghmann, Albert Heidrich, Eva Hellmis, Óscar Rodriguez Faba, José Luís Domínguez‐García, Romain Mathiéu, Marc Colombel, Franck Bladou, Xavier Artignan, Nikhil Vasdev, Rajendra Shimpi, Valentina Guadalupi, Rosa Tambaro, Zuzana Sirotovà, Massimiliano Spada, Andrea Necchi, Hiroomi Nakatsu, Eiji Kikuchi, Nobuaki Shimizu, Kent Kanao, Makoto Sumitomo, Yushi Naito, Won Sik Ham, Seung-Il Jung, H.K. Ha, Kwan Joong Joo, Ja Hyeon Ku, Ho Kyung Seo, Seok Joong Yun, Anna Kołodziej, Janusz Ławiński, David Morris, Siamak Daneshmand, Badar M. Mian, Eugene Lee
Abstract
•Erdafitinib prolonged RFS versus intravesical chemotherapy in papillary-only FGFR-altered BCG-treated high-risk NMIBC.•At median follow-up of 13.4 months, median RFS was not reached for erdafitinib and was 11.6 months for chemotherapy.•The observed RFS benefit for erdafitinib was further reflected by the 6- and 12-month RFS rates and subgroups tested.•In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy.•These trial results validate FGFR inhibition as a promising treatment approach for NMIBC. BackgroundTreatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) with disease recurrence after bacillus Calmette–Guérin (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 methodsPatients 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.ResultsStudy enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 to erdafitinib (n = 49) and chemotherapy (n = 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 = 0.0008). In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy.ConclusionsErdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, high-risk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for radical cystectomy. Treatment options are limited for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) with disease recurrence after bacillus Calmette–Guérin (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 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. Study enrollment was discontinued due to slow accrual. Seventy-three patients were randomized 2 : 1 to erdafitinib (n = 49) and chemotherapy (n = 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 = 0.0008). In this population, safety results were generally consistent with known profiles for erdafitinib and chemotherapy. Erdafitinib prolonged RFS compared with intravesical chemotherapy in patients with papillary-only, high-risk NMIBC harboring FGFR alterations who had disease recurrence after BCG therapy and refused or were ineligible for radical cystectomy.