Erdafitinib vs Chemotherapy in Previously Treated, FGFR-Mutated Advanced Urothelial Carcinoma

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As reported in The New England Journal of Medicine by Yohann Loriot, MD, PhD, and colleagues, cohort 1 of the phase III THOR trial has shown improved overall survival with erdafitinib vs chemotherapy in patients with locally advanced, unresectable, or metastatic urothelial carcinoma with erdafitinib-susceptible FGFR3/2 alterations who received previous PD-1/PD-L1 inhibitor therapy. These results were also presented at the European Society for Medical Oncology (ESMO) Congress 2023 (Abstract 2362MO).

Yohann Loriot, MD, PhD

Yohann Loriot, MD, PhD

Study Details

In cohort 1 of the open-label trial, 266 patients from sites in 23 countries were randomly assigned beginning in August 2018 to receive 21-day cycles of daily erdafitinib at 8 mg, with a pharmacodynamically guided increase to 9 mg on day 14 (n = 136), or investigator’s choice of docetaxel at 75 mg/m2 or vinflunine at 320 mg/m2 every 3 weeks (n = 130) until disease progression or unacceptable toxicity. All patients had disease progression after one or two previous treatments including a PD-1 or PD-L1 inhibitor. Overall, 59.6% of patients in the erdafitinib group and 48.5% in the chemotherapy group were White; 27.2% and 30.8% were Asian. The primary endpoint was overall survival.

Cohort 2 of the THOR trial compared erdafitinib vs pembrolizumab in patients who had not previously received an anti–PD-1 or anti–PD-L1 agent. The cohort 2 results were also presented at the ESMO Congress 2023 (Abstract 2359O) and simultaneously published in the Annals of Oncology.

Overall Survival  

Median follow-up was 15.9 months. Median overall survival was 12.1 months (95% confidence interval [CI] = 10.3–16.4 months) in the erdafitinib group vs 7.8 months (95% CI = 6.5–11.1 months) in the chemotherapy group (hazard ratio [HR] = 0.64, 95% CI = 0.47–0.88, P = .005). Rates at 6 and 12 months were 85% vs 66% and 51% vs 38%, respectively.

Objective response was observed in 35.3% vs 8.5% of patients. Median progression-free survival was 5.6 months (95% CI = 4.4–5.7 months) in the erdafitinib group vs 2.7 months (95% CI = 1.8–3.7 months) in the chemotherapy group (HR = 0.58, 95% CI = 0.44–0.78, P < .001).  Subsequent anticancer therapy was received by 32.4% of patients in the erdafitinib group and 36.9% of the chemotherapy group.


  • Erdafitinib significantly prolonged overall survival vs chemotherapy.
  • Median overall survival was 12.1 vs 7.8 months.

Adverse Events

Grade 3 or 4 treatment-related adverse events occurred in 45.9% of patients in the erdafitinib group and 46.4% of the chemotherapy group; the most common were palmar-plantar erythrodysesthesia syndrome (9.6%), stomatitis (8.1%), onycholysis (5.9%), and hyperphosphatemia (5.2%) in the erdafitinib group and neutropenia (13.4%) and anemia (6.2%) in the chemotherapy group. Treatment-related serious adverse events occurred in 13.3% vs 24.1% of patients; treatment-related adverse events led to treatment discontinuation in 8.1% vs 13.4%; and treatment-related death occurred in one patient (0.7%) in the erdafitinib group, due to sudden death, and in six patients (5.4%) in the chemotherapy group, due to febrile bone marrow aplasia and septic shock in two patients and atypical pneumonia and febrile neutropenia in one patient each.

The investigators concluded, “Erdafitinib therapy resulted in significantly longer overall survival than chemotherapy among patients with metastatic urothelial carcinoma and FGFR alterations after previous anti–PD-1 or anti–PD-L1 treatment.”

Arlene O. Siefker‑Radtke, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author for The New England Journal of Medicine article.

Disclosure: The study was funded by Janssen Research and Development. For full disclosures of the study authors, visit

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