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Clinical Trial
. 2022 Feb;23(2):248-258.
doi: 10.1016/S1470-2045(21)00660-4. Epub 2022 Jan 11.

Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study

Arlene O Siefker-Radtke  1 , Andrea Necchi  2 , Se Hoon Park  3 , Jesús García-Donas  4 , Robert A Huddart  5 , Earle F Burgess  6 , Mark T Fleming  7 , Arash Rezazadeh Kalebasty  8 , Begoña Mellado  9 , Sergei Varlamov  10 , Monika Joshi  11 , Ignacio Duran  12 , Scott T Tagawa  13 , Yousef Zakharia  14 , Sydney Akapame  15 , Ademi E Santiago-Walker  15 , Manish Monga  15 , Anne O'Hagan  15 , Yohann Loriot  16 ; BLC2001 Study Group
Collaborators, Affiliations
Clinical Trial

Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study

Arlene O Siefker-Radtke et al. Lancet Oncol. 2022 Feb.

Abstract

Background: Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, was shown to be clinically active and tolerable in patients with advanced urothelial carcinoma and prespecified FGFR alterations in the primary analysis of the BLC2001 study at median 11 months of follow-up. We aimed to assess the long-term efficacy and safety of the selected regimen of erdafitinib determined in the initial part of the study.

Methods: The open-label, non-comparator, phase 2, BLC2001 study was done at 126 medical centres in 14 countries across Asia, Europe, and North America. Eligible patients were aged 18 years or older with locally advanced and unresectable or metastatic urothelial carcinoma, at least one prespecified FGFR alteration, an Eastern Cooperative Oncology Group performance status of 0-2, and progressive disease after receiving at least one systemic chemotherapy or within 12 months of neoadjuvant or adjuvant chemotherapy or were ineligible for cisplatin. The selected regimen determined in the initial part of the study was continuous once daily 8 mg/day oral erdafitinib in 28-day cycles, with provision for pharmacodynamically guided uptitration to 9 mg/day (8 mg/day UpT). The primary endpoint was investigator-assessed confirmed objective response rate according to Response Evaluation Criteria In Solid Tumors version 1.1. Efficacy and safety were analysed in all treated patients who received at least one dose of erdafitinib. This is the final analysis of this study. This study is registered with ClinicalTrials.gov, NCT02365597.

Findings: Between May 25, 2015, and Aug 9, 2018, 2328 patients were screened, of whom 212 were enrolled and 101 were treated with the selected erdafitinib 8 mg/day UpT regimen. The data cutoff date for this analysis was Aug 9, 2019. Median efficacy follow-up was 24·0 months (IQR 22·7-26·6). The investigator-assessed objective response rate for patients treated with the selected erdafitinib regimen was 40 (40%; 95% CI 30-49) of 101 patients. The safety profile remained similar to that in the primary analysis, with no new safety signals reported with longer follow-up. Grade 3-4 treatment-emergent adverse events of any causality occurred in 72 (71%) of 101 patients. The most common grade 3-4 treatment-emergent adverse events of any cause were stomatitis (in 14 [14%] of 101 patients) and hyponatraemia (in 11 [11%]). There were no treatment-related deaths.

Interpretation: With longer follow-up, treatment with the selected regimen of erdafitinib showed consistent activity and a manageable safety profile in patients with locally advanced or metastatic urothelial carcinoma and prespecified FGFR alterations.

Funding: Janssen Research & Development.

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Conflict of interest statement

Declaration of interests EFB has received grants or contracts from Pfizer and Astellas Pharma; honoraria from Exelixis and Bayer; and stocks or stock options from Exelixis, Becton Dickinson, Calithera Biosciences, Gilead Sciences, Medtronic, Clovis Oncology, and Macrogenics, outside of the submitted work. ID has received grants or contracts from Roche/Genentech, AstraZeneca, and Astellas Pharma; consulting fees from Roche/Genentech, MSD Oncology, Bayer, Bristol Myers Squibb, Seattle Genetics, Pharmacyclics Janssen Oncology, and Novartis; honoraria from Bristol Myers Squibb, Ipsen, Roche/Genentech, Janssen Oncology, MSD Oncology, Astellas Pharma, and EUSA Pharma; and has been reimbursed for travel, accommodations, or expenses from Roche/Genentech, AstraZeneca Spain, and Ipsen, outside of the submitted work. MTF has received consulting fees from Janssen Oncology; honoraria from Genentech and Janssen Oncology; and has been reimbursed for travel, accommodations, or expenses from Medivation/Astellas and Genentech, outside of the submitted work. JG-D has received consulting fees from Bristol Myers Squibb and Clovis Oncology; honoraria from Roche, Bristol Myers Squibb, AstraZeneca, PharmaMar, GlaxoSmithKline, Amgen, Clovis Oncology, and Janssen-Cilag; and other financial or non-financial interests from Pfizer, Bristol Myers Squibb, Roche, AstraZeneca, Merck, GamaMabs Pharma, and InvitroCue, outside of the submitted work. RAH has received personal fees from Aspen Parkside Hospital, during the conduct of the study; consulting fees from Bristol Myers Squibb, Roche, Merck Sharp & Dohme, Janssen Oncology, Nektar, and Bayer; honoraria from Janssen Oncology; support for attending meetings or travel from Janssen Oncology, Roche/Genentech, MSD Oncology, and Nektar; other financial or non-financial interests from Merck Sharp & Dohme, Roche, Bristol Myers Squibb, and Janssen; has patents planned, issued, or pending from Janssen; and has a leadership or fiduciary role at Cancer Clinic London Limited Liability Partnership, outside of the submitted work. MJ has received consulting fees from Sanofi; and other financial interests from AstraZeneca and Pfizer, outside of the submitted work. YL has received consulting fees from Janssen, Astellas Pharma, Roche, AstraZeneca, MSD Oncology, Clovis Oncology, Seattle Genetics, and Bristol Myers Squibb; and has been reimbursed for accommodations or expenses from Astellas Pharma, Janssen Oncology, Roche, AstraZeneca, MSD Oncology, Clovis Oncology, Seattle Genetics, and Bristol Myers Squibb, outside of the submitted work. BM has received consulting fees from Pfizer, Roche, AstraZeneca, Bayer, Astellas Pharma, and Janssen, and for an immediate family member from Roche, Pfizer, and Amgen; support for attending meetings or travel from Janssen-Cilag and for an immediate family member from Roche; and other financial or non-financial interests from Roche, Janssen, and Bayer, outside of the submitted work. MM received personal fees from Janssen Oncology, during the conduct of the study. AN received personal fees from Bayer, during the conduct of the study; consulting fees from Merck Sharp & Dohme, Roche, Bayer, AstraZeneca, Clovis Oncology, Janssen, Seattle Genetics/Astellas, Bristol Myers Squibb, GlaxoSmithKline, and Ferring; honoraria from Roche, Merck, AstraZeneca, Janssen, Foundation Medicine, and Bristol Myers Squibb; support for attending meetings or travel from Roche, Merck Sharp & Dohme, AstraZeneca, Janssen, and Rainier Therapeutics; stocks or stock options for an immediate family member from Bayer; and other financial or non-financial interests from Merck Sharp & Dohme, AstraZeneca, and Ipsen, outside of the submitted work. AO'H received personal fees from Janssen, during the conduct of the study. AES-W received personal fees form Janssen, during the conduct of the study. AOS-R received support from the National Institutes of Health, Michael and Sherry Sutton Fund for Urothelial Cancer, Janssen, Takeda, Bristol Myers Squibb, BioClin Therapeutics, Nektar, Merck Sharp & Dohme, and Basilea; consulting fees from Janssen, Merck, National Comprehensive Cancer Network, Bristol Myers Squibb, AstraZeneca, Bavarian Nordic, Seattle Genetics, Nektar, Genentech, EMD Serono, Mirati Therapeutics, and Basilea; and has patents planned, issued, or pending related to molecular testing in muscle invasive bladder cancer, outside of the submitted work. STT has received consulting fees from Medivation, Astellas Pharma, Dendreon, Janssen, Bayer, Genentech, Endocyte, Immunomedics, Karyopharm Therapeutics, Abbvie, Tolmar, QED Therapeutics, Amgen, Sanofi, Pfizer, Clovis Oncology, Novartis, Genomic Health, and Point Biopharma; support for attending meetings or travel from Sanofi, Immunomedics, and Amgen; and other financial or non-financial interests from Lilly, Sanofi, Janssen, Astellas Pharma, Progenics, Millennium, Amgen, Bristol Myers Squibb, Dendreon, Rexahn Pharmaceuticals, Bayer, Genentech, Newlink Genetics, Inovio Pharmaceuticals, AstraZeneca, Immunomedics, Novartis, Aveo, Boehringer Ingelheim, Merck, Stem CentRx, Karyopharm Therapeutics, Abbvie, Medivation, Endocyte, Exelixis, and Clovis Oncology, outside of the submitted work. YZ has received consulting fees from Roche/Genentech, Eisai, Amgen, Castle Biosciences, Novartis, Exelixis, Pfizer, Cardinal Health, Bayer, Janssen, TTC Oncology, and Clovis Oncology; and support for attending meetings or travel from Newlink Genetics, outside of the submitted work.

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