Erdafitinib approved in Europe for FGFR3-positive urothelial carcinoma

The European Commission (EC) has approved erdafitinib (Balversa) as a once-daily monotherapy for the treatment of adult patients with unresectable or metastatic urothelial carcinoma who harbor FGFR3 genetic alterations and have previously received at least 1 line of therapy containing a PD-1 or PD-L1 inhibitor in the unresectable or metastatic treatment setting.¹

A long-term extension period of the trial is currently underway following the clinical cut-off date from the final analysis of each cohort.

“Bladder cancer is one of Europe’s most common cancers and the need for innovative treatment options for people living with unresectable or metastatic urothelial carcinoma remains high,” said Yohann Loriot, MD, PhD, of the Institut Gustave Roussy and University of Paris-Saclay, France, in a news release on the approval.¹ “Erdafitinib is a novel, targeted therapy that has been shown to significantly improve overall and progression-free survival for patients with FGFR3 alterations, who, until now, have had limited options available.”

The EC’s approval of erdafitinib follows a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use recommending approval of the therapy in June 2024. Erdafitinib also received US FDA approval in January 2024 for patients with locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 alterations whose disease has progressed on or after at least 1 line of prior systemic therapy. This indication excludes patients who, despite being eligible, have not received treatment with PD-1/PD-L1 checkpoint inhibitors.

The EC approval is supported by data from cohort 1 of the phase 3 THOR trial (NCT03390504), in which erdafitinib was shown to extend overall survival (OS) and progression-free survival (PFS) vs chemotherapy in patients with FGFR2/3-altered metastatic urothelial cancer who had previously received an anti–PD-(L)1 therapy.²

Specifically, at 1-year, the OS in the erdafitinib arm was 12.1 months, compared with 7.8 months in the chemotherapy arm, translating to a 36% reduction in the rate of death (HR, 0.64; 95% CI, 0.44-0.93; P = .0050). Based on the interim analysis, the independent monitoring committee recommended stopping the study, unblinding the data, and having patients cross over from chemotherapy to erdafitinib.

Erdafitinib also demonstrated meaningful improvements on the trial’s secondary end points, with a median PFS of 5.6 months in the erdafitinib arm vs 2.7 months in the chemotherapy arm (HR, 0.58; 95% CI, 0.41-0.82; P = .0002). The confirmed overall response rate (ORR) was 35.3% in the erdafitinib arm compared with 8.5% in the chemotherapy arm.

Regarding safety, 13.3% of patients in the erdafitinib arm and 24.1% of patients in the chemotherapy arm experienced a serious treatment-related adverse event (TRAEs). Grade 3 or higher AEs were experienced by 45.9% and 46.4% of patients in the erdafitinib and chemotherapy arms, respectively. TRAEs leading to treatment discontinuation occurred in 8.1% of patients who received erdafitinib vs 13.4% of patients who received chemotherapy. TRAEs leading to death occurred in 1 patient who received erdafitinib and 6 patients who received chemotherapy.

Overall, THOR is a phase 3, randomized, open-label, multicenter study, open to patients with unresectable or metastatic urothelial carcinoma who progressed on or following 2 prior lines of therapy. Patients were screened for selected FGFR alterations and were assigned to 2 cohorts based on prior anti–PD-(L)1 treatment.

Those with prior anti–PD-(L)1 therapy (cohort 1 for this analysis) were randomly assigned 1:1 to receive erdafitinib or investigator’s choice of chemotherapy. Erdafitinib was given orally at a starting dose of 8 mg once daily for 21 days in a 21-day cycle. Chemotherapy was given as either docetaxel 75 mg/m2 or vinflunine 320 mg/m2 every 3 weeks.

Treatment was continued until disease progression, intolerable toxicity, or withdrawal of consent. The primary end point for the trial was OS, with secondary end points of PFS, ORR, patient-reported outcomes, safety, and pharmacokinetics.

The median age of patients in the erdafitinib arm was 66 years (range, 32-85). Most were men (70.6%), White (59.6%), and had the presence of visceral metastases (74.3%), with 22.8% being in the liver. Nearly all patients had an ECOG performance status of 0 or 1 (91.2%).

A long-term extension period of the trial is currently underway following the clinical cut-off date from the final analysis of each cohort.

"The EC approval of erdafitinib reflects our unwavering commitment to transforming outcomes for people living with unresectable or metastatic urothelial carcinoma,” concluded Kiran Patel, MD, vice president of clinical development, solid tumors at Johnson & Johnson Innovative Medicine, in the news release.¹ “We look forward to continuing our research and development efforts to bring new hope and improved outcomes to more patients in the future.”

References

1. European Commission approves BALVERSA (erdafitinib) for adult patients with unresectable or metastatic urothelial carcinoma. News release. Janssen Cilag International NV. Published online and accessed August 23, 2024. https://www.globenewswire.com/en/news-release/2024/08/23/2934847/0/en/European-Commission-approves-BALVERSA-erdafitinib-for-adult-patients-with-unresectable-or-metastatic-urothelial-carcinoma.html

2. Loriot Y, Matsubara N, Park SH, et al. Phase 3 THOR study: results of erdafitinib (erda) versus chemotherapy (chemo) in patients (pts) with advanced or metastatic urothelial cancer (mUC) with select fibroblast growth factor receptor alterations (FGFRalt). J Clin Oncol. 2023;41(suppl 17):LBA4619