Abstract 625P
Background
TMPRSS2-ERG gene fusion is the most frequent alteration in prostate cancer (PC) and is associated with AR-regulated ERG overexpression. In castration-resistant PC (CRPC) we found a distinct correlation between TMPRSS2-ERG expression and taxane-resistance depending on treatment sequence. Here, we explore whether TMPRSS2-ERG affects outcomes of patients (pts) with metastatic hormone sensitive PC (mHSPC).
Methods
We conducted a multicenter, retrospective, biomarker study that included 218 mHSPC pts: 125 received androgen deprivation (ADT) + Docetaxel (DX) and 93 received ADT only. TMPRSS2-ERG expression was analyzed in primary tumors mRNA by nCounter technology (NanoString) by evaluating 5’/3’ imbalance probes designed over through ERG gene. TMRPSS2-ERG expression was correlated with CRPC free survival (CRPC-FS) and overall survival (OS) by Kaplan Meier and multivariate Cox modeling.
Results
ADT+DX and ADT only cohorts were followed up for 50.6 and 47.9 months (mo), respectively. In the whole population, TMPRSS2-ERG expression was independently associated with longer median CRPC-FS (21.1 vs 16.0 mo; hazard ratio [HR] 0.665 CI 0.5-0.9 p=0.01) and OS (66.4 vs 43.2 mo; HR 0.582 95%CI 0.4-0.8 p=0.004), and significant interaction between treatment (ADT/ADT+DX) and TMPRSS2-ERG detection was found (p=0.044). When segregating according to treatment, in patients treated with ADT only, TMPRSS2-ERG expression correlated with improved median CRPC-FS (19.7 vs 12.6 mo; HR 0.499 CI 0.32-0.78, P=0.0022) and OS (59.9 vs 39.2 mo; HR 0.511 CI 0.32-0.81, p=0.0045). In the multivariate analysis, TMPRSS2-ERG was an independent prognostic factor for both CRPC-FS (HR 0.448 CI 0.3-0.7, p=0.001) and OS (HR 0.463 CI 0.3-0.7, p=0.001). There was no statistical difference in CRPC-FS and OS according to TMPRSS2-ERG status in the ADT+DX population.
Conclusions
TMPRSS2-ERG expression associates with longer time to CRPC and OS in mHSPC treated with ADT only, but not in those treated with ADT+DX. Further characterization of TMRPSS2-ERG in the context of different treatments for mHSPC is warranted to elucidate its role as a predictive biomarker and potentially assist treatment selection.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Funded by a grant from Janssen Pharmaceuticals, number 212082PCR4056. ISCIII and ERDF ( PI18/174). CERCA Programme/Generalitat de Catalunya.
Disclosure
L. Ferrer: Financial Interests, Institutional, Invited Speaker: Pfizer; Financial Interests, Institutional, Invited Speaker: Kyowa Kirin. A. Font Pous: Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: PieRre-Fabre; Financial Interests, Institutional, Funding: Astellas; Financial Interests, Personal, Advisory Board: Jannsen; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: Ipsen; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Funding: Sanofi; Financial Interests, Personal, Funding: Jannsen. A. Rodriguez-Vida: Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: BMS; Financial Interests, Personal, Other: Jannsen; Financial Interests, Personal, Other: Astellas; Financial Interests, Personal, Other: Bayer; Financial Interests, Personal, Other: CLOVIS; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Sanofi; Financial Interests, Personal, Funding: TAKEDA; Financial Interests, Personal, Funding: Pfizer; Financial Interests, Personal, Funding: Merck. M. Domenech Santasusana: Financial Interests, Personal, Advisory Board: Sanofi. M. Figols Gorina: Financial Interests, Personal, Funding: Pfizer; Financial Interests, Personal, Funding: BMS; Financial Interests, Personal, Funding: Merck; Financial Interests, Personal, Funding: Sanofi; Financial Interests, Personal, Funding: Novartis; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Sanofi. M.A. Climent Duran: Financial Interests, Personal, Funding: BMS; Financial Interests, Personal, Funding: Astellas; Financial Interests, Personal, Funding: Jannsen; Financial Interests, Personal, Funding: MSD; Financial Interests, Personal, Funding: Sanofi; Financial Interests, Personal, Funding: Bayer; Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Funding: Novartis; Financial Interests, Personal, Funding: Ipsen; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: EUNSA; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Jannsen; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Ipsen. S. Cros Costa: Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: Tesaro; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Jannsen; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: BMS; Financial Interests, Personal, Other: Merck. I. Chirivella: Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Jannsen. E. Gonzalez-Billalabeitia: Financial Interests, Personal, Invited Speaker: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Invited Speaker: Jannsen. J. Carles Galceran: Financial Interests, Personal, Advisory Board: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Johnson & Johnson; Financial Interests, Personal, Advisory Board: MSD Oncology; Financial Interests, Personal, Advisory Board: Novartis (AAA); Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Astellas Pharma; Financial Interests, Personal, Speaker’s Bureau: Bayer; Financial Interests, Personal, Speaker’s Bureau: Johnson & Johnson; Financial Interests, Personal, Funding: BMS; Financial Interests, Personal, Funding: Ipsen; Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Funding: AstraZeneca; Financial Interests, Institutional, Funding: AB Science; Financial Interests, Institutional, Funding: Aragon Pharmaceuticals; Financial Interests, Institutional, Funding: Arog Pharmaceuticals; Financial Interests, Institutional, Funding: Astellas Pharma; Financial Interests, Institutional, Funding: AstraZeneca AB; Financial Interests, Institutional, Funding: Aveo Pharmaceuticals INC; Financial Interests, Institutional, Funding: Bayer AG; Financial Interests, Institutional, Funding: Blueprint Medicines Corporation; Financial Interests, Institutional, Funding: BN Immunotherapeutics Inc; Financial Interests, Institutional, Funding: Boehringer Ingelheim España; Financial Interests, Institutional, Funding: S.A.; Financial Interests, Institutional, Funding: Bristol-Myers Squibb International Corporation (BMS); Financial Interests, Institutional, Funding: Clovis Oncology, INC; Financial Interests, Institutional, Funding: Cougar Biotechnology Inc; Financial Interests, Institutional, Funding: Deciphera Pharmaceuticals LLC; Financial Interests, Institutional, Funding: Exelixis Inc; Financial Interests, Institutional, Funding: F. Hoffmann-La Roche Ltd; Financial Interests, Institutional, Funding: Genentech Inc; Financial Interests, Institutional, Funding: Glaxosmithkline; Financial Interests, Institutional, Funding: Incyte Corporation; Financial Interests, Institutional, Funding: Janssen-Cilag International NV; Financial Interests, Institutional, Funding: Karyopharm Therapeutics Inc.; Financial Interests, Institutional, Funding: Laboratoires Leurquin Mediolanum SAS; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Medimmune; Financial Interests, Institutional, Funding: Millennium Pharmaceuticals; Financial Interests, Institutional, Funding: Nanobiotix SA; Financial Interests, Institutional, Funding: Novartis Farmacéutica, S.A; Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Funding: S.L.U; Financial Interests, Institutional, Funding: Puma Biotechnology, INC; Financial Interests, Institutional, Funding: Sanofi-Aventis, S.A; Financial Interests, Institutional, Funding: SFJ Pharma Ltd. II; Financial Interests, Institutional, Funding: Teva Pharma S.L.U.; Financial Interests, Personal, Funding: BMS; Financial Interests, Personal, Funding: Ipsen; Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Funding: AstraZeneca. O. Reig Torras: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Funding: Ipsen; Financial Interests, Personal, Funding: Pfizer. B. Mellado: Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Funding: Bayer; Financial Interests, Personal, Funding: Jannsen; Financial Interests, Personal, Funding: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Jannsen; Financial Interests, Personal, Speaker’s Bureau: Astellas; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: BMS. All other authors have declared no conflicts of interest.