Full enrollment results from cohort 1 of the phase III randomized THOR trial of erdafitinib versus chemotherapy in FGFR-altered advanced urothelial carcinoma.
Abstract
Background
Cohort 1 of the phase III THOR trial met the primary endpoint of significantly longer overall survival (OS) with erdafitinib versus chemotherapy in patients with metastatic urothelial carcinoma (mUC) and select FGFR3/2 alterations who have progressed after prior anti-PD-(L)1 treatment. We present efficacy and safety results for the full cohort 1 at the end-of-study data cut-off (final database lock: 7 June 2024). PATIENTS AND
Methods
Adults with mUC with susceptible FGFR3/2 alterations who had progression after 1-2 prior treatments that included an anti-PD-(L)1 were randomly assigned 1 : 1 to receive erdafitinib or investigator's choice of chemotherapy (docetaxel or vinflunine). The primary endpoint was OS and progression-free survival (PFS) and objective response rate (ORR) were key secondary endpoints.
Results
At the end of data collection, median follow-up was 21.0 months for erdafitinib and 18.0 months for chemotherapy for the 278 patients in the fully enrolled THOR cohort 1 (erdafitinib, n = 143; chemotherapy, n = 135). Median OS remained significantly longer with erdafitinib versus chemotherapy [12.1 versus 8.7 months, hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.48-0.86, P = 0.0031]. Erdafitinib also showed sustained improvements over chemotherapy in PFS (median 5.4 versus 2.7 months, HR 0.59, 95% CI 0.45-0.77, P < 0.0001) and ORR (46.9% versus 12.6%, relative risk 3.74, 95% CI 2.31-6.04, P < 0.001). Grade 3-4 treatment-emergent adverse events occurred in 67.6% of patients in the erdafitinib group and 65.8% in the chemotherapy group. Erdafitinib was associated with fewer treatment-related serious adverse events (AEs) (12.7% versus 24.8%), treatment-related deaths (0.7% versus 6.0%), and treatment-related AEs that led to discontinuations (9.2% versus 14.5%) compared with chemotherapy.
Conclusions
At the end of data collection, erdafitinib continued to demonstrate survival and clinical response benefit versus chemotherapy, consistent with the primary analysis. No new safety signals were observed. These mature data support the use of erdafitinib in patients with advanced/mUC and susceptible FGFR3 alterations after PD-(L)1 inhibition.