ASCO 2023 - Urinary tract cancers - Evidence of superiority of targeted therapy over standard of care

ASCO 2023

Urinary tract cancers - Evidence of superiority of targeted therapy over standard of care

The THOR trial, coordinated by Dr. Yohann Loriot, Deputy Head of Gustave Roussy's Department of Therapeutic Innovation and Early Trials, was presented in a first-of-its-kind session at ASCO 2023. This multicenter, randomized phase 3 trial shows major benefits of erdafitinib on overall survival in a cohort of patients with metastatic bladder and upper urinary tract cancers and FGFR2 and FGFR3 gene abnormalities (mutations or fusions), compared with chemotherapy. With a 36% reduction in the risk of death and a 45% response rate, this targeted therapy is to become a standard in the management of this type of cancer.

Abstract n° LBA 4619 orally presented by Dr. Yohann Loriot on June 5, 2023

Affecting almost 15 000 people each year in France, urothelial cancer, which develops in the bladder or upper urinary tract, is the most common urological cancer after prostate cancer. Nearly 5 000 deaths are attributable to urothelial cancer occurring each year in France. First-line treatment is based on chemotherapy and immunotherapy. Nevertheless, relapse remains frequent in a majority of patients whose tumor is discovered at an advanced stage or has become metastatic. What's more, some 15-20 % of patients have an abnormality (mutation or fusion) in the FGFR2 or FGFR3 (Fibroblast Growth Factor Receptor) genes.

Clinical benefit on overall survival

The THOR study builds on the results of a previous Phase 2 trial led by Dr. Loriot, demonstrating the efficacy of erdafitinib in patients with metastatic urothelial cancer. This new targeted therapy is an inhibitor of FGFRs.

The international phase 3 THOR trial included 266 patients with metastatic urothelial cancer carrying a mutation or fusion of the FGFR2 or FGFR3 gene. All patients had previously received at least one line of immunotherapy. After randomization, patients were treated either with daily oral erdafitinib (8 mg) or with chemotherapy of the investigator's choice (docetaxel or vinflunine). The primary endpoint was overall survival. 

Intermediate results showed a 36% reduction in the risk of death in the erdafitinib group, with a median overall survival prolongation of one year. The response rate was also superior, with a result of 45.5% for patients in whom the targeted therapy had been administered versus 12% in the chemotherapy group. Erdafitinib also significantly improved median progression-free survival (5.6 months versus 2.7 months). « The survival benefit was observed irrespective of the type of abnormality (mutation or fusion), the number of previous lines of treatment received, the presence or absence of metastases, and the type of primary tumor (bladder or upper urinary tract cancer), » explains Dr. Yohann Loriot, main investigator of the study.

The THOR study could pave the way for its approval in Europe. In France, this targeted therapy is currently only available on a compassionate basis.