Early-Line Infigratinib for Patients with FGFR3-Altered Metastatic Urothelial Carcinoma - Expert Commentary

The standard-of-care first-line systemic therapy for metastatic urothelial cancer (mUC) remains platinum-based chemotherapy. Post-platinum options included immune checkpoint inhibitors, fibroblast growth factor receptor (FGFR) inhibitors in patients with FGFR2 or FGFR3 genomic alterations, or antibody-drug conjugates. However, the best sequence of these systemic therapies is unknown. Furthermore, it is unclear if patients with FGFR2 or FGFR3 alterations should receive FGFR inhibitor at an early stage of their disease course.


A recent study published by Lyou et al. in Clinical Genitourinary Cancer investigated the treatment sequence and the efficacy of infigratinib, a fibroblast growth factor receptor (FGFR) 1–3 inhibitor in patients with FGFR3-altered metastatic urothelial cancer.

The investigators recruited 67 patients with mUC who were resistant to or ineligible for platinum-based chemotherapy and had FGFR3 mutations or fusions. Only patients with WHO performance status 0–2 were included. Patients with prior therapy with FGFR or MEK inhibitors were excluded. All participants were given open-label infigratinib once daily in a 28-day cycle (21 days on, seven days off), commencing at a dose of 125 mg a day with two-level dose reductions to 100 or 75 mg. Thirteen patients received infigratinib as an early-line therapy, while 54 patients had previously received one or more lines of treatment, mainly platinum-based chemotherapy.

The investigators found that early-line infigratinib had a 31% objective response rate (ORR), while infigratinib after one or more previous lines of treatment (LOT) had a 24% ORR. In addition, no significant differences in treatment-emergent adverse events were observed among the two settings. These results suggest that infigratinib had significant efficacy in patients with mUC, independent of the LOT. Therefore, infigratinib should be evaluated in randomized trials in earlier settings.

Platinum-based chemotherapy in the first-line setting is not always feasible due to different factors, including medical comorbidities, organ function, potential toxicity, and patient preference. Treatment with FGFR inhibitors represents a possible early alternative to platinum-based chemotherapy in patients who cannot tolerate chemotherapy and have tumors with FGFR-activating alterations or patients who have contraindications to immune checkpoint inhibitors.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York

Reference:

  1. Lyou Y, Rosenberg JE, Hoffman-Censits J, Quinn DI, Petrylak D, Galsky M, et al. Infigratinib in Early-Line and Salvage Therapy for FGFR3-Altered Metastatic Urothelial Carcinoma. Clin Genitourin Cancer. 2021 Oct 13. doi: 10.1016/j.clgc.2021.10.004.. PMID: 34782263.

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