Erdafitinib treatment in Brazilian patients with metastatic urothelial carcinoma (mUC): real-world evidence from an Expanded Access Program

Abstract

Background: Erdafitinib is the first targeted therapy approved for the treatment of patients with metastatic urothelial carcinoma (mUC). Approval was based on a phase II single-arm trial that demonstrated significant activity of erdafitinib in patients with tumors harboring FGFR2/3 alterations. In Brazil, an Expanded Access Program (EAP) provided patients with early access to erdafitinib prior to market authorization. The current report describes characteristics and outcomes of patients with mUC on erdafitinib therapy. Methods: Patients with mUC that failed first- and second-line systemic therapies were screened for FGFR2/3 alterations in primary or metastatic tumor tissues. Patients with FGFR2/3 alterations were selected to receive erdafitinib at the standard dosing schedule and were followed prospectively to evaluate the efficacy and safety outcomes. Results: From 19 April 2019, through 13 March 2020, 47 patients with mUC from 10 Brazilian centers were tested for FGFR2/3 alterations. Alterations in FGFR2/3 were found in 12 patients (25.5%) and all of them were eligible for the EAP. Four patients (33%) had partial response, while two patients (17%) had stable disease. Progressive disease, the best response, was observed in five patients (42%). At a median follow-up of 16.2 months, the median time to treatment failure (TTF) was 2.8 months. When considering only patients with objective response, the median TTF was 5.3 months. Adverse events (AEs) were reported for any grade and grade 3 or higher in 10 patients (83%) and 5 patients (42%), respectively. The most common AE was hyperphosphatemia. Conclusion: This first real-world evidence report of heavily treated patients with mUC confirms the efficacy and safety of erdafitinib in a disease setting with a lack of treatment options.

Erdafitinib treatment in metastatic urothelial carcinoma: a real-world analysis

“…The efficacy of erdafitinib therapy seen in the present study is similar to a Brazilian real life prospective study of an expanded access program ( 1 ), where erdafitinib was given as third line of therapy, and associated with a clinical benefit (response or stable disease) of 50% and a median time to treatment failure was 2.8 months.…”

“…The progression free survival and overall in the present study were shorter than those reported in the BCL2001 prospective trial (3,4). This may be due to the fact that a significant proportion of patients in the present study were treated with erdafitinib in a more advanced line setting (48% treated as third or fourth-line of therapy), similar to the Brazilian real life prospective study (1), and 40% of them were treated after both chemotherapy and immunotherapy. Furthermore, 36% had a decreased ECOG performance status of 2, and most were with high volume disease (80% with visceral metastases, and 4% with brain metastases).…”

“…Urothelial carcinoma is the second most common urological malignancy in the western world (1). Until recent years, the standard of care in the metastatic setting consisted only of platinum based chemotherapy in the first line setting, with limited activity (10% response rate and short overall survival) of chemotherapy as advanced treatment line (2)(3)(4).…”

“…Until recent years, the standard of care in the metastatic setting consisted only of platinum based chemotherapy in the first line setting, with limited activity (10% response rate and short overall survival) of chemotherapy as advanced treatment line (2)(3)(4). In 2017, immune checkpoint inhibitors were incorporated in the treatment paradigm, mainly in the post platinum based chemotherapy setting, but are associated with a durable clinical benefit only in a minority of patients (20% response rate) (1,2,5). Recently, two more therapies were FDA approved for these patients in the advanced treatment line, the FGFR inhibitor erdafitinib, and the antibody-drug conjugates enfortumab vedotin (demonstrating improvement of overall survival) and sacituzumab govitecan (based on a phase 2 trial) (6)(7)(8).…”

THEM6: A Novel Molecular Biomarker Predicts Tumor Microenvironment, Molecular Subtype, and Prognosis in Bladder Cancer

“…Though THEM6 has the potential to become a new option for diagnosis and treatment target for BLCA and along with the development of molecular target drugs, the current research progress has entered the preclinical or clinical research stage [ 50 ]. Because of the enormous difficulties in assessing toxicity, as well as successful drug delivery systems, the clinical application of THEM6 inhibitor remains to be further confirmed.…”