Erdafitinib Demonstrates Improved Responses in FGFR-Altered Advanced Urothelial Carcinoma

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Targeted treatment with the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib improved responses and overall survival compared to standard chemotherapy for patients with advanced or metastatic urothelial carcinoma with FGFR alterations. Results from the phase III THOR trial, led by researchers at The University of Texas MD Anderson Cancer Center, were reported at the European Society of Medical Oncology (ESMO) Congress 2023.

"Metastatic urothelial cancer continues to challenge us with its absence of a cure, highlighting the need for innovative treatment approaches," said Arlene Siefker-Radtke, MD, Professor of Genitourinary Medical Oncology at MD Anderson and senior investigator on the trial. "This ongoing study presents compelling evidence that erdafitinib could potentially serve as a valuable targeted treatment option for individuals with FGFR alterations."

Arlene Siefker-Radtke, MD

Arlene Siefker-Radtke, MD

Genetic changes in FGFR are present in approximately 20% of patients with metastatic bladder cancer and up to 35% of patients with other urothelial cancers, including renal pelvis and ureter cancers. In 2019, erdafitinib was approved by the U.S. Food and Drug Administration for advanced FGFR-altered urothelial cancer based on the results of the phase II BLC2001 trial led by Dr. Siefker-Radtke. It was the first approved FGFR-targeted therapy and is the only approved FGFR-targeted option for advanced urothelial cancer.

The ongoing randomized THOR trial—conducted at 121 sites in 23 countries—evaluated the efficacy and safety of erdafitinib in patients with metastatic urothelial carcinoma and selected FGFR gene alterations. Patients were screened for the presence of FGFR gene alterations and assigned to two cohorts based on prior treatment with platinum-containing chemotherapy or immune checkpoint inhibitors.

Patients Treated With Prior Immunotherapy

In the study's first cohort, presented at the ESMO Congress 2023 (Abstract 2362MO) and simultaneously published in The New England Journal of Medicine, 266 patients who received prior treatment with immune checkpoint inhibitors were randomly assigned to receive either erdafitinib or chemotherapy. The median overall survival was 12.1 months and 7.8 months, respectively, corresponding to a 36% lower risk of death for those treated with erdafitinib. The overall survival benefit was seen across subgroups, including age, type of FGFR alteration, number of prior lines of treatment, visceral metastasis, location of the primary tumor, and type of chemotherapy.

Further, erdafitinib achieved a median progression-free survival of 6 months compared to 3 months for chemotherapy. Nearly half (46%) of patients treated with erdafitinib had an objective response, while 12% on the chemotherapy arm had an objective response. The data from this cohort was first presented at the 2023 ASCO Annual Meeting (Abstract LBA4619).

Outcomes in Immunotherapy-Naive Patients

In the second cohort, also presented at the ESMO Congress 2023 (Abstract 2359O) and simultaneously published in the Annals of Oncology, 351 patients who had not received prior immunotherapy were randomly assigned to receive either erdafitinib or the anti–PD-1 therapy pembrolizumab. There was no statistically significant difference in overall survival between the treatment arms, as erdafitinib resulted in similar survival compared to immunotherapy in patients who received prior pembrolizumab.

Erdafitinib did achieve a median progression-free survival of 4.4 months compared to 2.7 months for pembrolizumab. Further, 40% of patients treated with erdafitinib had an objective response, while just 21.6% on the pembrolizumab arm had an objective response. There was a shorter duration of response with erdafitinib (4.3 months) than with pembrolizumab (24.4 months).

“The data from this new cohort provides early evidence suggesting there may be important impacts from the sequence of treatments for an FGFR3-altered urothelial cancer,” Dr. Siefker-Radtke said. “Even though most primary FGFR-altered urothelial tumors are immunologically cold, it is possible that metastatic tumors may not share the same features. Perhaps these patients could benefit from combining erdafitinib with an immune checkpoint inhibitor.”

Safety and Next Steps

Treatment-related adverse events across both cohorts were manageable and consistent with the known safety profile of erdafitinib.

The impact of erdafitinib on the overall survival of patients with metastatic urothelial carcinoma and FGFR alterations highlights the importance of conducting molecular tests to identify FGFR alterations in individuals with metastatic urothelial cancer.

Further work is necessary to understand the impact of combining and sequencing erdafitinib with a checkpoint inhibitor. There may be a role for erdafitinib in patients with visceral crisis where rapid response and symptom improvement is indicated, thanks to its higher response rate.

Disclosure: The THOR trial was supported by Janssen Research & Development, LLC. For full disclosures of the study authors, visit and

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®.