WASHINGTON -- FDA on Friday for treating metastatic bladder cancer in adults with FGFR3 or FGFR2 alterations, representing the first targeted therapy for the disease.
Indicated for patients that progress on platinum-based chemotherapy, use of the agent will require a companion diagnostic device to confirm alteration status.
"FGFRs [fibroblast growth factor receptors] regulate important biological processes including cell growth and division during development and tissue repair," Richard Pazdur, MD, the agency's top oncology official explained in a statement announcing the accelerated approval. "This drug works by targeting genetic alterations in FGFRs."
The phase II multicenter, open-label study that led to erdafitinib's approval included 87 patients with locally advanced or metastatic bladder cancer. Patients were required to have progressed on chemotherapy and harbor alterations in FGFR3 or FGFR2. About one-quarter of patients had previously received anti-PD-1/PD-L1 checkpoint inhibitors.
Treatment with erdafitinib yielded an overall response rate of 32.2%, including patients that failed on immune checkpoint inhibitors, and two patients achieved a complete response. Median duration of response was 5.4 months. None of the six patients with FGFR2 fusion genes responded to treatment, according to a from drugmaker Janssen.
The FDA warned of the risk of serious eye problems, and said patients should receive eye exams while on treatment.
A host of adverse events and reactions were observed in the trial, including stomatitis, fatigue, diarrhea, onycholysis, decreased appetite, dysgeusia, alopecia, palmar-plantar erythrodysesthesia syndrome, constipation, decreased phosphate, abdominal pain, nausea, musculoskeletal pain, as well as dry mouth, skin, and eyes. Laboratory abnormalities (≥20%) included increased levels of phosphate, creatinine, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, and calcium; as well as decreased levels of sodium, albumin, hemoglobin, magnesium, and phosphate.
Over two-thirds of patients required dose interruptions and 53% required dose reductions.
Grade ≥3 adverse events or reactions included stomatitis, nail dystrophy, palmar-plantar erythrodysesthesia syndrome, paronychia, nail disorders, keratitis, onycholysis, and hyperphosphatemia.