medwireNews: Oral erdafitinib is associated with significantly improved recurrence-free survival (RFS) compared with intravesical chemotherapy for patients with non-muscle-invasive bladder cancer (NMIBC) and specific fibroblast growth factor receptor (FGFR) alterations who have progressed after bacillus Calmette-Guérin (BCG) therapy, show THOR-2 trial findings.
The cohort 1 data were presented at the ESMO Congress 2023 in Madrid, Spain, by James Catto, from the University of Sheffield in the UK, and simultaneously reported in the Annals of Oncology.
The study screened 1092 patients with recurrent, papillary-only, high grade (Ta/T1) NMIBC who were unwilling or unable to undergo radical cystectomy and who had at least one specified mutation in FGFR3 or a specified FGFR2 or FGFR3 fusion.
James Catto explained that recruitment to the study was slow and halted after enrolment of only 73 of the 240 planned patients. This was partially due to global shortages of BCG therapy and resulted in the trialists developing a novel BCG-experienced definition as a “pragmatic solution”. This described patients who had received at least five of six full doses of an initial induction course but necessarily the maintenance treatment or second course in line with the usual stringent criteria for BCG-unresponsive disease.
Session discussant Michiel van der Heijden, from the Netherlands Cancer Institute in Amsterdam, said that the BCG-experienced definition reflected “the real-world where patients struggle to get all the BCG cycles that are recommended” and is therefore “entirely reasonable”.
After a median follow-up of 13.4 months, median RFS was not reached for the 49 patients who were randomly assigned to receive oral erdafitinib 6 mg/day versus 11.6 months for the 24 patients who instead received an investigator’s choice of either intravesical mitomycin C or intravesical or hyperthermic gemcitabine chemotherapy. This gave a hazard ratio for recurrence or death of 0.28 in favour of the pan-FGFR tyrosine kinase inhibitor.
The RFS rate was 96% with erdafitinib at 6 months versus 73% with chemotherapy, falling to 77% and 41%, respectively, at 12 months. Preplanned analysis also favoured erdafitinib across all subgroups including by age, tumour stage and BCG treatment criteria.
Turning to the safety profile, James Catto said that the adverse events (AEs) were “generally consistent” with prior reports for both erdafitinib and intravesical chemotherapy.
He observed that the original protocol was for oral erdafitinib up-titrated from a starting dose of 8 mg/day to 9 mg/day, as per the recommended dose for advanced disease. This was changed to a continuous dose of 6 mg/day after three of the first four patients required dose interruptions and two discontinued treatment due to AEs, highlighting “the low acceptability for systemic toxicity in patients with NMIBC,” he commented.
Overall, 28.6% of erdafitinib-treated patients had AEs leading to discontinuation versus none of the controls. There were no treatment-related deaths.
Most AEs were at grade 1 or 2; erdafitinb at 6 mg/day was associated with nail toxicity (77.6%, 6.1% at ≥grade 3), hyperphosphatemia (73.5%), eye toxicities excluding central serous retinopathy (59.2% and 4.1% at grade ≥3), skin toxicity (51.0%), dry mouth (46.9%), stomatitis (40.8% and 10.2%) and central serous retinopathy (38.8% and 4.1%).
James Catto summarised that oral erdafitinib achieved a 72% improvement in RFS and is a “valid approach in the NMIBC population” but acknowledged that even at the lower dose, “oral erdafitinib tolerability was challenging” and pointed to findings for the TAR-210 intravesical drug delivery system for erdafitinib, also being presented at the ESMO Congress 2023.
In a comment to medwireNews, he said that the “most worrying” AEs were retinal and the most common were “nail, skin and mouth issues” and that “local administration into the bladder should avoid these.”
Michiel van der Heijden agreed that the “burden” of systemic erdafitinib toxicity was too high to balance only a delay in recurrence rather a cure, but he acknowledged that “intravesical erdafitinib may be an interesting alternative.”
James Catto added that THOR-2 demonstrated that randomised study design, offering a small number of standard care options was feasible with NMIBC and “makes the case for wider biomarker testing” in this population.
References
LBA102 - Catto J, Tran B, Rouprêt M, et al. THOR-2 cohort 1: Results of erdafitinib (ERDA) vs intravesical chemotherapy (chemo) in patients (pts) with high-risk non–muscle-invasive bladder cancer (HR NMIBC) with select fibroblast growth factor receptor alterations (FGFRALT) who received prior bacillus calmette-guérin (BCG) treatment.
Catto J, Tran B, Rouprêt M, et al. Erdafitinib in BCG-treated high-risk non-muscle-invasive bladder cancer. Ann Oncol; Advance online publication, 20 October 2023.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2023 Springer Healthcare Ltd, part of the Springer Nature Group