Patients with FGFR-altered advanced urothelial cancer benefit from erdafitinib after anti-PD-L1 failure, THOR study reports.
Checkpoint inhibitors are standard of care both in first- and second-line setting in patients with advanced or metastatic urothelial cancer. Treatment options after progression on checkpoint inhibitors are limited and only 30% of patients receive subsequent anti-cancer treatment after anti-PD-L1 treatment. FGFR gene alterations are common in advanced/metastatic urothelial cancer, and the pan-FGFR tyrosine kinase inhibitor erdafitinib showed promising clinical activity in a single-arm phase 2 trial.
THOR (NCT03390504) is a randomized, confirmatory phase 3 trial assessing whether erdafitinib improves survival over chemotherapy in patients with FGFR-altered advanced/metastatic urothelial cancer who progressed on or after 1 or more prior lines of treatment including anti-PD-L1 therapy. Yohann Loriot, MD, PhD, presented the results at the 2023 ASCO Annual Meeting, held June 2-6 in Chicago.
The study randomly assigned 266 patients 1:1 to receive erdafitinib or chemotherapy (ie, docetaxel or vinflunine); 78 patients had received one prior line of treatment, and 187 had received two prior lines of treatment. The primary endpoint was overall survival (OS); key secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and safety.
The study met its primary endpoint. The median OS for erdafitinib was superior to chemotherapy: 12.1 versus 7.8 months (HR, 0.64; P=0.0005). The OS benefit of erdafitinib was seen across all subgroups. In addition, erdafitinib significantly improved median PFS: 5.6 versus 2.7 months (HR, 0.58; P=0.0002). ORR in the erdafitinib arm was 45.6% (6.6% complete responders) compared with 11.5% (0.8% complete responders) in the chemotherapy arm.
Safety profiles were consistent with the known profiles of erdafitinib and chemotherapy. Of patients treated with erdafitinib, 8.1% discontinued therapy due to treatment-related adverse events. Of patients treated with chemotherapy, 13.4% discontinued therapy due to treatment-related adverse events. Adverse events of interest in the erdafitinib arm were nail, skin, and eye disorders, and central serous retinopathy.
“The results of the THOR trial support the clinical efficacy of erdafitinib as the standard-of-care option for patients with advanced/metastatic FGFR-altered urothelial cancer after anti-PD-L1 treatment. In addition, these results support molecular testing for FGFR alterations in all patients with advanced/metastatic urothelial cancer,” concluded Dr. Loriot.
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