Phase 3 THOR Study: Erdafitinib Provides OS Benefit Over Chemotherapy

New data from the phase 3 THOR study were presented at the European Society for Medical Oncology Congress 2023 by Dr. Yohann Loriot, of Gustave Roussy in France. The randomized, phase 3 study assessed whether erdafitinib could provide an overall survival (OS) benefit over chemotherapy in patients with metastatic urothelial carcinoma (mUC) who progressed after 1 to 2 prior therapies, including anti-PD-L1.

Select FGFR alterations (FGFRalt) are seen in approximately 20% of patients with mUC. Erdafitinib was analyzed in this patient population due to its use as a pan-FGFR tyrosine kinase inhibitor for patients with locally advanced or mUC with susceptible FGFR3/2alt who have progressed after platinum-containing chemotherapy.

Patients enrolled in the study were 18 years of age or older, with unresectable advanced/mUC and select FGFR3/2alt (mutations/fusions), an Eastern Cooperative Oncology Group performance status of 0 to 2, adequate organ function, and progression on or after 1 to 2 prior lines of systemic therapy that included anti-PD-L1.

Each patient was randomized 1:1 to receive either erdafitinib 8 mg (with pharmacodynamically guided up-titration to 9 mg) daily or investigator’s choice of chemotherapy (docetaxel or vinflunine) every 3 weeks until disease progression or intolerable toxicity. The primary end point was OS, and secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.

A total of 266 patients were involved in the study, with 136 patients receiving erdafitinib and 130 receiving chemotherapy. The median patient age was 67 years, and median follow-up was 16 months. The median OS of the erdafitinib and chemotherapy arms was 12.1 and 7.8 months, respectively (hazard ratio, 0.64; 95% CI, 0.47-0.88). An OS benefit was seen across all study subgroups, and erdafitinib improved PFS (6 months vs 3 months) and ORR (46% vs 12%) over chemotherapy.

The most frequent treatment-related adverse events (TRAEs) were hyperphosphatemia (79%), diarrhea (55%), and stomatitis (46%) in patients who underwent erdafitinib treatment. The most frequent TRAEs in patients who underwent chemotherapy were anemia (28%), alopecia (21%), and nausea (20%). In each arm, 46% of patients experienced grade 3 or 4 TRAEs. One patient in the erdafitinib arm experienced TRAEs that resulted in death compared with 6 patients in the chemotherapy arm.

Erdafitinib was found to significantly improve OS and provide a consistent OS benefit over chemotherapy in patients with FGFRalt advanced/mUC after prior anti-PD-L1 treatment. No new safety signals were observed.

Researchers support the use of erdafitinib for the treatment of this patient population.