Dr Catto on the Utility of Erdafitinib in High-Risk nMIBC With FGFR Alterations

James Catto, MB, ChB, PhD, FRCS, professor, urological surgery, clinical medicine, NIHR Research Professor, School of Medicine and Population Health, University of Sheffield, honorary consultant urological surgeon, Sheffield Teaching Hospitals, NHS Trust, honorary senior clinical research fellow, the University of Oxford, honorary clinical professor, Division of Surgery and Interventional Science, University College London, discusses the utility of erdafitinib (Balversa) in patients with high-risk non–muscle-invasive bladder cancer (nMIBC) with select FGFRalterations who have received prior treatment with Bacillus Calmette–Guérin (BCG).

At the 2023 ESMO Congress, Catto expanded on findings from the phase 2 THOR-2 trial (NCT04172675), which evaluated treatment with erdafitinib vs intravesical chemotherapy in patients with previously treated, FGFR-altered nMIBC. Investigators found that erdafitinib, when given orally, reduced the risk of disease recurrence or death by 72% vs its comparator. Notably, the median recurrence-free survival was not reached with erdafitinib (95% CI, 16.9-not evaluable) vs 11.6 months (95% CI, 6.4-20.1) with intravesical chemotherapy, and the estimated hazard ratio was 0.28 (95% CI, 0.1-0.6; P = .0008).

Although the primary treatment for patients with nMIBC following resection is BCG therapy, approximately half of patients who receive BCG are unresponsive to this therapy and have limited treatment alternatives, Catto begins. Notably, the standard treatment approach for patients with BCG-unresponsive disease is radical cystectomy, a major surgical operation that significantly affects patients' quality of life, he states. Therefore, the THOR-2 investigators focused on exploring treatment options for patients in this population, Catto says.

Erdafitinib is an active TKI/pan-FGFR inhibitor that is FDA approved for patients with metastatic or locally advanced bladder cancer with FGFR2/3 alterations that has progressed on platinum-containing chemotherapy, he notes. In THOR-2, investigators examined a group of patients whose primary tumors were screened for FGF alterations. Those with FGFR2/3alterations were randomly assigned to receive either orally administered erdafitinib or conventional intravesical chemotherapy. The follow-up data now extend to 13.4 months, and the response rates with erdafitinib have been highly encouraging, he emphasizes.

However, it is important to note the challenges associated with the tolerability of erdafitinib, he continues. All patients treated in THOR-2 experienced adverse effects with erdafitinib, and 28.6% of patients had to discontinue the treatment because of toxicities. In the long term, erdafitinib appears to be a highly effective treatment, he states. Nevertheless, the safety findings from THOR-2 raise the question of whether an orally administered systemic treatment is suitable for a localized disease, Catto concludes.