Novel FGFR3 Inhibitor May Be a New Treatment Option for Metastatic Urothelial Carcinoma

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Previous early-phase clinical studies have demonstrated that BGJ398 was active and well tolerated in a variety of FGFR-altered cancers.
Previous early-phase clinical studies have demonstrated that BGJ398 was active and well tolerated in a variety of FGFR-altered cancers.

BGJ398 therapy led to good clinical responses and may be a new treatment modality among patients with metastatic urothelial carcinoma (mUC) characterized by fibroblast growth factor receptor (FGFR3)-alterations, according to findings published in Cancer Discovery.1

Although targeted therapy with anti-PD-L1/PD-1 agents (eg, pembrolizumab, atezolizumab) improved survival outcomes among patients with mUC compared with standard platinum-based chemotherapy, treatment response rates are discouraging. Previous early phase clinical studies have demonstrated that BGJ398, a novel agent that targets FGFR (a commonly occurring alteration in UC), was active and well tolerated in a variety of FGFR-altered cancers.

In this phase 1 study, researchers enrolled 67 previously treated patients with mUC who had FGFR3 mutations and treated them with oral BGJ398 125 mg daily; all had failed, were intolerant of, or were contraindicated for platinum-based therapies. Patients received MRI or CT scans at baseline and every 8 weeks thereafter. After therapy discontinuation, disease progression was assessed every 4 months for 1 year, and survival for up to 2 years.

Results showed that the overall response rate, including complete (CR) and partial responses (PR), was 25.4%, and the disease control rate was 64.2%.

Patients who achieved CR or PR had an estimated median duration of response of 5.06 months (95% CI, 3.91-7.36), and the estimated median duration of stable disease among patients whose best response was stable disease was 2.0 months (95% CI, 1.84-3.45).

The estimated median progression-free survival was 3.75 months (95% CI, 3.09-5.39) with 46 progressions and 5 deaths. The estimated median overall survival was 7.75 months (95% CI, 5.65-11.60) with 41 events.

The most frequently reported treatment-related adverse effects included constipation, elevated creatinine, fatigue, decreased appetite, and hyperphosphatemia.

The authors concluded that “for selected patients, FGFR3-targeted therapies may represent a viable alternative strategy. Alternatively, combinatorial strategies with immunotherapy could be considered, but require further preclinical and clinical validation.”

Reference

  1. Pal SK, Rosenberg JE, Hoffman-Censits, JH, et al. Efficacy of BGJ398, a fibroblast growth factor receptor 1–3 inhibitor, in patients with previously treated advanced urothelial carcinoma with FGFR3 alterations [published online May 30, 2018]. Cancer Discov. doi: 10.1158/2159-8290

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