STUDY DESIGN

In metastatic urothelial cancer (mUC), checkpoint inhibitors are used in the first- and second-line settings.¹ However, only 30% of mUC patients respond to these agents.¹ After progression on programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors, about 30% of patients received subsequent anticancer treatment in real-world practice due to limited treatment options.¹ To address this gap, the THOR trial, a confirmatory, randomized, phase 3 study, was conducted to assess whether erdafitinib, a selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor (TKI), could provide survival benefits over chemotherapy in a patient population with FGFR alterations (FGFRalt) mUC patients after anti-PD-1/PD-L1 treatment.¹  

In the THOR trial, 266 adult patients with FGFR-alternated mUC which progressed on or after treatment with PD-1/PD-L1 inhibitors were randomized 1:1 to receive erdafitinib 8mg once daily with pharmacodynamically guided uptitration to 9mg (n=136) or chemotherapy of docetaxel or vinflunine once every 3 weeks (n=130).¹ The primary endpoint was overall survival (OS).¹ The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and safety.¹ Patients were followed for a median of 15.9 months.¹

The findings showed that patients receiving erdafitinib had an improved OS (12.1 months vs. 7.8 months) and a reduced risk of death compared with chemotherapy (HR=0.64; 95% CI: 0.47-0.88; p=0.005).¹ The subgroup analysis demonstrated a consistent OS benefit across different subgroups.¹ Due to the obvious survival benefit of erdafitinib, the study was stopped as per the independent data monitoring committee’s (IDMC) recommendation with the unblinding of data and switching patients from chemotherapy to erdafitinib.¹ Moreover, patients receiving erdafitinib had an improved PFS and ORR, as well as a consistent safety profile with manageable adverse events (AEs) of erdafitinib.¹

FINDINGS

“Overall, this study supported the clinical efficacy of erdafitinib as the standard of care option for patients with mUC and FGRalt after anti-PD-1/PD-L1 treatment”

 

^{Dr. Yohann Loriot
Department of Cancer Medicine,
INSERM U981,
Gustave Roussy,
Universite Paris-Saclay,
Villejuif, France}