Phase 2 study of neoadjuvant FGFR inhibition and androgen deprivation therapy prior to prostatectomy
- Author(s)
- Liow, E; Howard, N; Jung, CH; Pope, B; Campbell, BK; Nguyen, A; Kerger, M; Ruddle, JB; Anton, A; Thomas, B; Chu, K; Dundee, P; Peters, JS; Costello, AJ; Ryan, AS; Hovens, CM; Tran, B; Corcoran, NM;
- Journal Title
- Clinical Genitourinary Cancer
- Publication Type
- epub ahead of print
- Abstract
- BACKGROUND: Disease recurrence is common following prostatectomy in patients with localised prostate cancer with high-risk features. Although androgen deprivation therapy increases the rates of organ-confined disease and negative surgical margins, there is no significant benefit on disease recurrence. Multiple lines of evidence suggest that (Fibroblast Growth Factor/Fibroblast Growth Factor Receptor) FGF/FGFR-signalling is important in supporting prostate epithelial cell survival in hostile conditions, including acute androgen deprivation. Given the recent availability of oral FGFR inhibitors, we investigated whether combination therapy could improve tumour response in the neo-adjuvant setting. METHODS: We conducted an open label phase II study of the combination of erdafitinib (3 months) and androgen deprivation therapy (4 months) in men with localised prostate cancer with high-risk features prior to prostatectomy using a Simon's 2 stage design. The co-primary endpoints were safety and tolerability and pathological response in the prostatectomy specimen. The effect of treatment on residual tumours was explored by global transcriptional profiling with RNA-sequencing. RESULTS: Nine patients were enrolled in the first stage of the trial. The treatment combination was poorly tolerated. Erdafitinib treatment was discontinued early in six patients, three of whom also required dose interruptions/reductions. Androgen deprivation therapy for 4 months was completed in all patients. The most common adverse events were hyperphosphataemia, taste disturbance, dry mouth and nail changes. No patients achieved a complete pathological response, although patients who tolerated erdafitinib for longer had smaller residual tumours, associated with reduced transcriptional signatures of epithelial cell proliferation. CONCLUSIONS: Although there was a possible enhanced anti-tumour effect of androgen deprivation therapy in combination with erdafitnib in treatment naïve prostate cancer, the poor tolerability in this patient population prohibits the use of this combination in this setting.
- Publisher
- Elsevier
- Keywords
- Fgf; High-risk prostate cancer; Pathological respose; Safety; Surgery
- Research Division(s)
- Personalised Oncology
- PubMed ID
- 35688680
- Publisher's Version
- https://doi.org/10.1016/j.clgc.2022.05.007
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2022-06-17 09:28:50
Last Modified: 2022-06-17 09:53:25