Therapeutics: Erdafitinib for bladder cancer

Published: 17-May-2019

Urothelial cancer, which most often occurs in the bladder, is one of the more common types of cancer, but the prognosis is not good: the relative five-year survival rate for Stage IV disease is just 5%

In particular, those patients who have fibroblast growth factor receptor (FGFR) mutations have a poor prognosis. These mutations occur in about 10–20% of patients with metastatic urothelial cancer.

The response rate to existing drugs is poor and their tumours may not respond to treatment with immune checkpoint inhibitor drugs. A new drug, developed by Johnson & Johnson in collaboration with Astex, shows great potential in these patients.

Erdafitinib is an orally available pan-FGFR inhibitor designed to block the FGFR receptor tyrosine kinases that are thought to lead to increased tumour cell growth and survival.1 A companion diagnostic is used to identify patients whose tumours have this mutation and who, therefore, might benefit from treatment.

In a first-in-human Phase I dose finding study, 65 patients with advanced solid tumours were given escalating doses of erdafitinib, ranging from 0.5–12 mg administered continuously daily, or doses of 10 or 12 mg of the drug administered on a seven days on, seven days off schedule.2

The most common treatment-emergent adverse events included hyperphosphataemia, asthenia, dry mouth, constipation, nail toxicity and decreased appetite. One dose limiting toxicity, grade 3 ALT elevation, occurred with a 12 mg daily dose.

It had linear, dose-proportional pharmacokinetics and a half-life of 50–60 hours. Among the 23 evaluable patients, there were four confirmed responses and one partial. A further 16 patients achieved stable disease.

In a Phase I, open label, single arm, dose escalation study, 19 patients were enrolled into escalating dose cohorts of 2, 4 or 6 mg, with a daily dosing schedule of 21-day cycles, or 10 or 12 mg on a seven days on/seven days off schedule.3

The maximum tolerated dose was not reached and no grade 3 or higher treatment-emergent adverse events were observed.

In an open label Phase II clinical trial, the efficacy and safety of erdafitinib was evaluated in 99 adult patients who had locally advanced or metastatic urothelial cancer and the appropriate FGFR mutations within their tumours.4

Subjects were treated according to an optimised dosing schedule using pharmacodynamically guided dose up-titration. The starting dose was 8 mg/day, with the possibility of increasing the dose to 9 mg/day based on serum phosphate levels.

Of the patients, 12% were naïve to chemotherapy; of the rest, 43% had received two or more previous lines of therapy and more than three quarters of the subjects had visceral metastases.

There was a 40% confirmed overall response rate and a median progression-free survival of 5.5 months. The median overall survival was 13.8 months. The most common grade 3 adverse events were stomatitis, hand-foot syndrome and diarrhoea. Seven subjects dropped out of the trial because of treatment-related adverse events.


  1. T.P.S. Perera, et al., Mol. Cancer Ther. 16, 1010 (2017).
  2. J. Tabernero, et al., J. Clin. Oncol. 33, 3401 (2015).
  3. T. Nishina, et al., Invest. New Drugs 36, 424 (2018).
  4. A.O. Siefker-Radtke, J. Clin. Oncol. 36(Suppl.) Abst. 4503 (2018).

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