Phase 2 Study of Neoadjuvant FGFR Inhibition and Androgen Deprivation Therapy Prior to Prostatectomy.

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.

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.

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.

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.

Clinical genitourinary cancer. 2022 May 18 [Epub ahead of print]

Elizabeth Liow, Nicholas Howard, Chol-Hee Jung, Bernard Pope, Bethany K Campbell, Anne Nguyen, Michael Kerger, Jonathan B Ruddle, Angelyn Anton, Benjamin Thomas, Kevin Chu, Philip Dundee, Justin S Peters, Anthony J Costello, Andrew S Ryan, Christopher M Hovens, Ben Tran, Niall M Corcoran

Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Department of Medical Oncology, Monash Health, Melbourne, VIC, Australia., Urology Unit, Royal Melbourne Hospital, Parkville, VIC, Australia., Melbourne Bioinformatics, The University of Melbourne, Parkville, VIC, Australia., Melbourne Bioinformatics, The University of Melbourne, Parkville, VIC, Australia; Department of Medicine, School of Clinical Sciences, Monash University, VIC, Australia; Department of Surgery, University of Melbourne, Royal Melbourne Hospital, VIC, Australia., Department of Surgery, University of Melbourne, Royal Melbourne Hospital, VIC, Australia., Department of Surgery, University of Melbourne, Royal Melbourne Hospital, VIC, Australia; Australian Prostate Centre, North Melbourne, VIC, Australia., Urology Unit, Royal Melbourne Hospital, Parkville, VIC, Australia; Department of Surgery, University of Melbourne, Royal Melbourne Hospital, VIC, Australia., Department of Urology, Monash Health, Melbourne, VIC, Australia., Urology Unit, Royal Melbourne Hospital, Parkville, VIC, Australia; Department of Surgery, University of Melbourne, Royal Melbourne Hospital, VIC, Australia; Australian Prostate Centre, North Melbourne, VIC, Australia., TissuPath, Mount Waverley, VIC, Australia., Department of Surgery, University of Melbourne, Royal Melbourne Hospital, VIC, Australia; Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia., Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, VIC, Australia., Urology Unit, Royal Melbourne Hospital, Parkville, VIC, Australia; Department of Surgery, University of Melbourne, Royal Melbourne Hospital, VIC, Australia; Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia. Electronic address: .

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