A study into the pharmacodynamic biomarker effects of olaparib (PARP Inhibitor) ± degarelix (GnRH antagonist) given prior to radical prostatectomy (RP) CANCAP03.

• DOI: 10.1200/jco.2019.37.7_suppl.35
• Publication Date: 2019-03-07T21:20:50Z
• Authors: Simon Pacey; Mark David Linch; Howard Kynaston; Anne Warren; Alex Freeman; Ruth Tysoe; Greg Shaw; Krishna Narahari; Satish Kumar; Henno Martin; Bihani Kularatne; Vincent Gnanaprag...; Barry Davies; Josephine Khan; Ola Bratt; Harveer Dev; Charles Massie; Nimish Shah
• Keywords: Olaparib; PARP inhibitor; Tolerability; Clinical endpoint; Veliparib; Pharmacodynamics; Interim analysis

35 Background: Novel agents given prior to RP allows the study of drug effect(s) in primary human prostate cancer (PC), supporting future clinical development. Pre-clinical and data (mostly setting castration resistant PC) support PARP ± androgen inhibition as therapy for some patients (pt). We undertook a olaparib (O) degarelix (D) RP. Methods: 20 evaluable (pre post tissue available with 86% dose compliance) pt randomised 1:1 O or O+D. Primary endpoint: measure by IHC. Secondary endpoints were feasibility, safety, tolerability. Exploratory objectives: changes PSA, circulating tumour DNA & intra-tumoral immune cells. Men, due RP, high volume aggressive PC, consented treated (300mg bd) 15 days D (240mg once), Diagnostic biopsy collected. Adverse events (AE) graded according CTCAE v4 followed up resolution 6-weeks Results: 24 men recruited, 4 not (opted radiotherapy, surgery date altered, AE). Interim results are presented data. Conclusions: 2 weeks (± D) can be acceptable safety profile. analyses ongoing however, preliminary confirm PSA drop noted on both regimens. While expected O+D this is first report following short course single agent PARPi local/ hormone sensitive PC. Clinical trial information: NCT02324998. [Table: see text]