9PPlasma gene conversions after one cycle (C) abiraterone acetate (AA) for metastatic castration-resistant prostate cancer (mCRPC): A biomarker analysis of a multi-centre, international trial

Abstract Background A number of genomic alterations detected in plasma DNA have been associated with worse outcome in mCRPC (Jayaram et al Cancer Discov). We hypothesized that patients (pts) who harbored a genomic alteration that decreased after 1C of treatment derive treatment benefit and this would distinguish them from truly resistant pts. Methods Plasma DNA (128 C1 day (D) 1,134 C2 D1, and 41 progression [PD] from chemotherapy-naive mCRPC pts in a phase 2 study of AA (NCT01867710), recently reported (Attard et al, Jama Onc) were subjected to custom targeted-capture NGS. Assay was optimised and validated to detect pathogenic point mutations (PM), deletions and copy number alterations (CNA) inAR, TP53, RB1, PIK3CA and DNA repair deficient genes (DRD): BRCA1, BRCA2, FANCA, ATM, CHEK2, HDAC2, BRIP1, and PALB2. Pts were followed up for overall survival (OS) and radiographic progression-free survival (rPFS) (48 months). Results Pts were classified into 4 groups based on whether a gene alteration was detectable (+) or not (-) at C1D1 and C2D1 respectively. At C1D1, 49 pts (37.5%) had + alterations. Pts who converted from + to - (+/-) had similar outcomes as pts who remained - (-/-) and those that did not convert had worst outcomes (+/+) (Table). In matched C1D1 and PD samples pts with ARgain (G) at C1D1 were more ARG at PD (p =  Conclusions These findings suggest that tracking gene aberrations in plasma DNA could be an early marker of treatment efficacy. Clinical trial identification NCT01867710. Legal entity responsible for the study The authors. Funding Janssen Pharmaceuticals. Disclosure D. Shen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen Research and Development. A. Wingate: Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses: Janssens. C. Sternberg: Honoraria (self): Astellas Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Sanofi; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: Eisai; Advisory / Consultancy, Research grant / Funding (institution): Clovis Oncology; Advisory / Consultancy, Research grant / Funding (institution): Incyte; Advisory / Consultancy: Roche; Advisory / Consultancy: Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: Medscape; Advisory / Consultancy: UroToday; Advisory / Consultancy: Genentech; Advisory / Consultancy: Medivation; Research grant / Funding (institution): Exelixis. R. Jones: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas Pharma; Honoraria (self), Travel / Accommodation / Expenses: Janssen; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: MSD Oncology; Honoraria (self): BMS; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Novartis; Honoraria (self), Travel / Accommodation / Expenses: Ipsen; Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): Exelixis; Honoraria (self): Sanofi; Honoraria (self): Genentech; Honoraria (self): Eusa Pharma; Honoraria (self): Pharmacyclics. A. Berruti: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen-Cilag; Advisory / Consultancy, Research grant / Funding (institution): Astellas Pharma; Travel / Accommodation / Expenses: Sanofi. F. Lefresne: Honoraria (self), Research grant / Funding (self), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Johnson & Johnson. M. Lahaye: Honoraria (self), Advisory / Consultancy, Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: Janssen-Cilag. S. Thomas: Leadership role, Research grant / Funding (self), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment: Janssen Research and Development. S. Joshi: Honoraria (self), Travel / Accommodation / Expenses, Full / Part-time employment: Janssen Research and Development. M. Gormley: Travel / Accommodation / Expenses, Licensing / Royalties, Full / Part-time employment: Janssen Research and Development. B. Tombal: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas Pharma; Honoraria (institution), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ferring; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Takeda; Advisory / Consultancy: Steba Biotech; Honoraria (self): Myovant Sciences. A. Merseburger: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen-Cilag; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas Pharma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Honoraria (self): Roche; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): BMS; Honoraria (self): Eisai; Honoraria (self): Takeda; Honoraria (self): Pfizer; Honoraria (self), Research grant / Funding (self): Novartis; Research grant / Funding (institution): Clovis Oncology. D. Ricci: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Licensing / Royalties, Full / Part-time employment: Janssen. G. Attard: Honoraria (self), Honoraria (institution), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas Pharma; Advisory / Consultancy: Janssen-Cilag; Research grant / Funding (institution): Innocrin; Research grant / Funding (institution): Arno; Advisory / Consultancy, Travel / Accommodation / Expenses: Ventana Medical Systems; Travel / Accommodation / Expenses: Abbott Laboratories; Licensing / Royalties: ICR Rewards to Inventors; Honoraria (self), Travel / Accommodation / Expenses: Abbott; Advisory / Consultancy, Travel / Accommodation / Expenses: ESSA; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. All other authors have declared no conflicts of interest.