Episode 12: Erdafitinib versus chemotherapy and pembrolizumab in FGFRalt metastatic urothelial carcinoma

In this episode of ‘What’s New Doc’ in GU cancer, Prof Emmanuel Seront from UCL Louvain and Prof Christof Vulsteke from Maria Middelares Gent will discuss the THOR trial, focusing on two cohorts of metastatic urothelial carcinoma patients with FGFR alterations, treated with erdafitinib.

FGFR alterations are present in 20-35% of patients, making erdafitinib a viable treatment option for those who have failed chemotherapy, checkpoint inhibitors, or EV-pembrolizumab in the first-line setting.

The first cohort underwent randomization in a 1:1 ratio to receive either erdafitinib or chemotherapy. Results showed significantly higher median OS and median PFS in the erdafitinib group, with higher response rates and manageable safety profiles. This underscores erdafitinib’s efficacy following the failure of chemotherapy and checkpoint inhibition. Notably, FGFR alteration testing is crucial for patient selection.

The second cohort, following platinum-based chemotherapy failure, compared erdafitinib and pembrolizumab in a 1:1 randomization. Surprisingly, there was no clear winner, as both drugs yielded a median OS of approximately 11 months. However, erdafitinib demonstrated a higher response rate of 40% versus 20% for pembrolizumab and longer PFS, while pembrolizumab exhibited a longer median duration of response and fewer side effects.

The key takeaway from these trials is that with FGFR alterations and after chemotherapy failure, patients have the option of erdafitinib or pembrolizumab, with erdafitinib being preferable for rapid responses.

In the third-line setting, after platinum chemotherapy and checkpoint inhibition, the choices now include EV or erdafitinib. EV is preferred in the absence of FGFR alterations, while both drugs are viable options in the presence of FGFR alterations, with a slight preference for EV based on side effect profiles.

Although erdafitinib is not currently available, the results of these phase 3 trials should expedite its approval, offering a promising new therapeutic avenue for patients.