Exploring the THOR Study of Erdafitinib in Advanced Bladder Cancer

Arlene O. Siefker-Radtke, MD, professor of genitourinary medical oncology at the University of Texas MD Anderson Cancer Center in Houston, Texas, dives into the background and the cohorts included in the phase 3 THOR study (NCT03390504) which evaluated erdafitinib (Balversa) vs pembrolizumab (Keytruda) in pretreated patients with advanced or metastatic urothelial cancer with select fibroblast growth factor receptor (FGFR) alterations.

In January 2024, the FDA approved erdafitinib for the treatment of patients with locally advanced or metastatic urothelial cancer with FGFR3 genetic alterations who have experienced disease progression on or following at least 1 prior line of treatment, as supported by findings from the phase 3 THOR study.

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0:09 | The phase 3 THOR clinical trial was designed to meet an unmet need, where we were exploring the impact of FGFR targeted therapy in patients with metastatic urothelial cancer and pre-selected FGF alterations present on their cancer. This trial is unique in that we also try to explore the impact of sequencing. Would it be better to do or erdafitinib prior to receiving immunotherapy? And that was 1 cohort of the trial. We also had a second cohort of the trial, where we compared erdafitinib with single-agent taxanes in patients who had prior chemotherapy and immunotherapy.

0:56 | The original cohort of the THOR trial was presented at ASCO. We have a publication that came out in the New England Journal of Medicine. Because the trial was positive and showed that in patients with FGF alterations who receive prior treatment with chemotherapy and immunotherapy, erdafitinib significantly improved the median overall survival in that group of patients. It also had an improvement in progression-free survival and objective response rate. We do have level 1 evidence now that erdafitinib plays a role in the FGF-altered tumor, but to explore the impact of sequencing, we also had this second cohort of the clinical trial, where we took patients who had prior chemotherapy, but did not receive treatment with a prior immune checkpoint inhibitor.

1:54 | The reason for us designing this trial is that we noticed that FGF-altered tumors appeared to have an immunologically cold tumor microenvironment. They were often associated with very low PD-L1 expression levels, and this is the cohort of patients that were predicted to have a lesser degree of benefit with an immune checkpoint inhibitor. In the second cohort, we took patients who received prior chemotherapy, but no prior treatment with an immune checkpoint inhibitor, they must have had an FGF alteration present, and we randomized them between erdafitinib and pembrolizumab.