Results From THOR Study of Erdafitinib in FGFR-Altered Urothelial Cancer

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

Findings presented at the 2023 ESMO Congress showed that while the primary end point of superior overall survival was not met with erdafitinib, there were similar survival rates observed between erdafitinib and pembrolizumab in this patient population of those with anti-PD-(L)1-naïve metastatic urothelial carcinoma who harbor FGFR alterations.

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0:10 | The findings of this cohort were recently presented at ESMO, and what we saw when we compared erdafitinib vs pembrolizumab [was] enrichment for those PD-L1-low tumors. Over 90% of patients had a low CPS score of less than 10 and about 50% had a CPS score less than 1. Despite being an immunologically cold tumor, we saw similar outcomes, so the trial was negative, we did not show an improvement in overall survival.

0:46 | When we look at the shape of the survival curve, we saw early benefit from erdafitinib, which we think likely reflects its cytoreductive potential, it had a 40% objective response rate compared with a 21% objective response rate with pembrolizumab. However, responses with immunotherapy have more durability, and that was reflected in the latter half of the survival curve where we saw some durability of response. While erdafitinib had a higher response rate, those that do respond to a checkpoint inhibitor have durability that enhances patient outcomes.

1:30 | Even though the trial was a negative trial, and we did not show an improvement, survival was similar. While I would argue for the impact of sequencing, it is better to give erdafitinib in patients who have received a prior immune checkpoint inhibitor, I would also argue there are potentially patients where cytoreduction is essential. Perhaps they have a visceral crisis, significant symptoms, pain, discomfort, shortness of breath from lung metastases, or gross hematuria due to extensive tumor in the bladder. Those patients may need the cytoreduction that can be achieved with treatment with an FGF inhibitor.