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2018 ASCO: Erdafitinib Shows Activity in FGFR3-Mutated Urothelial Cancer

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Key Points

  • Treatment with erdafitinib met the primary objective with a 40% overall response rate, including complete response in 3% of patients and partial response in 37%. Among 22 patients who previously had been treated with checkpoint blockade inhibitors, erdafitinib treatment yielded an overall response in 59% of patients.
  • An additional 39% of patients had stable disease without progression.
  • Preliminary data from the trial indicate a median overall survival of 13.8 months.

In an international phase II trial led by researchers at The University of Texas MD Anderson Cancer Center, treatment with the oral FGFR inhibitor erdafitinib was well tolerated and achieved a robust response for patients with metastatic urothelial cancers harboring mutations in the FGFR3 gene. These findings were presented by Siefker-Radtke et al at the 2018 ASCO Annual Meeting (Abstract 4503). The results were also granted the Best of ASCO designation.

“Given the limited treatment options for urothelial cancer, we still have a long way to go to benefit our patients. Having a therapy with a response rate around 40%, with the convenience of being an oral medication, certainly fits an unmet need,” said Arlene O. Siefker-Radtke, MD, Professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine at MD Anderson.

For several decades, the standard of care for urothelial cancers has been chemotherapy with a cisplatin-based regimen, but five new checkpoint blockade inhibitors have been approved in recent years, explained Dr. Siefker-Radtke. Nevertheless, the overall response rate is just 15% to 20% with these immunotherapies, she said.

Erdafitinib is an oral medication that blocks activity of all FGFR proteins, including FGFR3. Genetic alterations in FGFR3 can be found in approximately 15% to 20% of patients with metastatic bladder cancer and are thought to drive development of the disease. Further, tumors with FGFR3 mutations do not appear to display signs of immune activation, and there is growing evidence suggesting these tumors may not respond as well to immunotherapy, explained Dr. Siefker-Radtke.

Trial Findings

For the international, open-label, phase II trial, 99 patients were enrolled and treated with a median of five cycles of the optimized erdafitinib regimen, consisting of 8 mg/d for 28 days, with escalation to 9 mg/d allowed in the absence of significant adverse events. All patients had metastatic or surgically unresectable urothelial cancer with a verified mutation in FGFR3 or fusion in FGFR2 or FGFR3. Previous treatment with chemotherapy and/or immune checkpoint inhibitors was allowed.

Treatment with erdafitinib met the primary objective with a 40% overall response rate, including complete response in 3% of patients and partial response in 37%. An additional 39% of patients had stable disease without progression. Preliminary data from the trial indicate a median overall survival of 13.8 months. Among 22 patients who previously had been treated with checkpoint blockade inhibitors, erdafitinib treatment yielded an overall response in 59% of patients.

Treatment-related adverse events were manageable, with 10% of patients discontinuing treatment due to symptoms. There were no treatment-related deaths and no grade 4 events. The most common adverse events were grade 1 and 2, including hyperphosphatemia (72 patients, grade ≥ 3 in 2 patients), stomatitis (54 patients, grade ≥ 3 in 9 patients), and diarrhea (37 patients, grade ≥ 3 in 4 patients).

“Erdafitinib treatment has been very tolerable. There have been few dose reductions, and most patients have been able to continue on treatment,” said Dr. Siefker-Radtke. “Even with evidence of high phosphate levels or other toxicities, usually a period of just holding the drug was enough to reduce symptoms.”

She continued, “We will need confirmation in future studies, but there may be more benefit from an FGFR-targeted therapy in patients with an FGFR alteration as compared to immunotherapy. It's an exciting time, as we are heading into the field of personalized therapy for urothelial cancer.”

A phase III trial currently underway is evaluating the efficacy of erdafitinib relative to chemotherapy or the checkpoint blockade inhibitor pembrolizumab (Keytruda) in patients with metastatic urothelial cancer and FGFR3 mutations. Based on the phase II study, the U.S. Food and Drug Administration granted a Breakthrough Therapy designation to erdafitinib earlier this year, which will expedite development and review of the drug for metastatic urothelial cancer.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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