(Urothelial Carcinoma) What Is the Objective Response Rate of Erdafitinib?

• August 31, 2019
• Reading time: 2 minutes

On July 25, 2019, Yohann Loriot published results in The New England Journal of Medicine from a Phase II clinical trial evaluating erdafitinib monotherapy — a FGFR1–4 tyrosine kinase inhibitor — in patients with locally advanced or metastatic urothelial carcinoma harboring fibroblast growth factor receptor (FGFR) gene mutations.

This Phase II open-label trial enrolled patients with FGFR-mutated locally advanced or metastatic urothelial carcinoma. Patients received erdafitinib 6–10 mg once daily in 28-day cycles. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS), overall survival (OS), and others.

FGFR mutations occur at high frequency in urothelial carcinoma, and patients with FGFR mutations may have suboptimal responses to immunotherapy. Based on Phase I data confirming the antitumor activity of FGFR1–4 tyrosine kinase inhibition in FGFR-mutated patients, this trial was initiated to confirm efficacy.

Patient Characteristics:

Efficacy Results:

The primary endpoint ORR was 40%: complete response 3%, partial response 37%, stable disease 39%. Median duration of treatment was 5.6 months; median time to tumor response was 1.4 months.

ORR by prior treatment: post-chemotherapy progression 40% / treatment-naive 42% / post-immunotherapy progression 59%.

ORR by number of prior regimens: 0 regimens 36% / 1 regimen 38% / 2 regimens 38% / 3 regimens 60% / 4 regimens 50%.

Secondary endpoints: median PFS 5.5 months; 12-month PFS rate 19%. Median OS 13.8 months; 12-month OS rate 55%.

Safety:

Overall adverse event rate was 100%; Grade 3–4 adverse events occurred in 67% of patients. Most common Grade 3–4 events were hyponatremia (11%), stomatitis (10%), and asthenia (7%). The most common reason for treatment discontinuation was disease progression.

Based on the Phase II trial results, Yohann Loriot concluded that erdafitinib achieved a 40% ORR in FGFR-mutated locally advanced or metastatic urothelial carcinoma patients, with Grade 3–4 adverse events occurring in more than half of patients.

Source: Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma (N Engl J Med 2019; 381:338–348 DOI: 10.1056/NEJMoa1817323)

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