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.
Keywords
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Article info
Publication history
Published online: May 18, 2022
Accepted:
May 15,
2022
Received in revised form:
May 9,
2022
Received:
April 25,
2022
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.
