Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study
Mené dans 14 pays sur 101 patients atteints d'un carcinome urothélial de stade localement avancé ou métastatique (durée médiane de suivi : 24 mois), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité de l'erdafitinib (un inhibiteur pan-FGFR)
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 centresin 14 countries across Asia, Europe, and North America. Eligible patients were aged18 years or older with locally advanced and unresectable or metastatic urothelialcarcinoma, at least one prespecified FGFR alteration, an Eastern Cooperative Oncology Group performance status of 0–2, andprogressive disease after receiving at least one systemic chemotherapy or within 12months of neoadjuvant or adjuvant chemotherapy or were ineligible for cisplatin. Theselected regimen determined in the initial part of the study was continuous once daily8 mg/day oral erdafitinib in 28-day cycles, with provision for pharmacodynamicallyguided uptitration to 9 mg/day (8 mg/day UpT). The primary endpoint was investigator-assessedconfirmed objective response rate according to Response Evaluation Criteria In SolidTumors version 1.1. Efficacy and safety were analysed in all treated patients whoreceived 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 wereenrolled 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-upwas 24·0 months (IQR 22·7–26·6). The investigator-assessed objective response ratefor 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-emergentadverse events of any causality occurred in 72 (71%) of 101 patients. The most commongrade 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-relateddeaths. Interpretation : With longer follow-up, treatment with the selected regimen of erdafitinib showed consistentactivity and a manageable safety profile in patients with locally advanced or metastaticurothelial carcinoma and prespecified FGFR alterations.