Abstract 1971P
Background
NE dedifferentiation is associated to clinical aggressiveness and resistance to androgen receptor (AR) inhibition in prostate cancer. We analyzed the correlation of a NE expression signature in non-castrate tumors with the clinical outcome of mCRPC patients treated with taxanes or AR signaling inhibitors (ARSI; abiraterone or enzalutamide).
Methods
Patients with mCRPC were retrospectively tested for a customized signature of 45 NE-related genes in total RNA from formalin-fixed paraffin-embedded non-castrate tumor samples by the nCounter platform (Nanostring Technologies). Patients were grouped as high and low NE profile according to the unsupervised clustering of gene expression data and correlated with treatment response and clinical outcome.
Results
Ninety-six patients were included, with a median follow-up of 20 (1.17-81.3) months. Median age was 69.2 (55.8-87.1) years. All patients received taxanes (68 docetaxel, 10 cabazitaxel and 18 both), 29 received ARSI as first line in CRPC and 53 received ARSI after taxanes. Patients classified as high NE expression profile (59 vs. 37 patients) were associated with a shorter time of CRPC development (median 12.6 vs. 30.8 mo, HR 3.3, 95%CI 2-5.5, P<0.001) and shorter OS from CRPC diagnosis (median 24.3 vs. 42.2 mo, HR 2.2, 95%CI 1.4-3.4, P=0.001). Regarding taxanes outcome, high NE profile patients correlated with lower PSA-PFS (HR 1.7, 95%CI 1.1-2.6, P=0.011), radiologic (RX)-PFS (HR 1.8, 95%CI 1.1-2.8, P=0.012) and overall survival (OS) (HR 1.7, 95%CI 1.1-2.6, P=0.009), and they were independently associated with shorter PSA-PFS (HR 1.8, 95%CI 1.1-3, P=0.023). In first-line ARSI-treated patients, high NE profile patients (15 vs. 14 patients) correlated with shorter PSA-PFS (HR 3, 95%CI 1.3-7, P=0.011), RX-PFS (HR 2.5, 95%CI 1-5.9, P=0.042) and OS (HR 5.8, 95%CI 2.3-14.9, P<0.001).
Conclusions
NE-related gene expression in non-castrate tumor samples is associated with adverse clinical outcome and both poor taxanes and ARSI benefit in mCRPC patients. Thus, molecular characterization of primary tumors may be useful to guide treatment strategies in mCRPC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Hospital Clínic de Barcelona.
Funding
Instituto de Salud Carlos III-Subdirección General de Evaluación y Fomento de la Investigación; European Regional Development Fund; CERCA Programme/Generalitat de Catalunya.
Disclosure
N. Jimenez: Travel/Accommodation/Expenses: Sanofi. O. Reig: Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Ipsen; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer. L. Ferrer-Mileo: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Pfizer; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Kyowa kirin. A. Font: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Janssen; Research grant/Funding (institution), Travel/Accommodation/Expenses: Astra-Zeneca; Research grant/Funding (institution), Travel/Accommodation/Expenses: Astellas Pharma; Research grant/Funding (institution): Pierre-Fabre. M. Domènech: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Travel/Accommodation/Expenses: Astellas Pharma; Travel/Accommodation/Expenses: Janssen. A. Rodríguez-Vida: Research grant/Funding (institution): MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Takeda; Advisory/Consultancy, Speaker Bureau/Expert testimony: Astellas Pharma; Speaker Bureau/Expert testimony: Astra-Zeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: Sanofi-Aventis; Advisory/Consultancy: Clovis. J. Carles: Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Johnson&Johnson; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Astellas Pharma; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Sanofi; Advisory/Consultancy: MSD; Advisory/Consultancy: Roche; Advisory/Consultancy: Astra-Zeneca; Speaker Bureau/Expert testimony: Asofarma. C. Suárez: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: EUSA Pharma; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: Novartis; Speaker Bureau/Expert testimony: Roche/Genentech; Speaker Bureau/Expert testimony: Astra-Zeneca; Travel/Accommodation/Expenses: Roche. N. Sala-González: Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen. A. Prat: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Daiichi Sankyo; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Nanostring technologies; Advisory/Consultancy: Puma; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Officer/Board of Directors: Breast International Group; Officer/Board of Directors: Solti's Foundation; Officer/Board of Directors: Actitud frente al cáncer Foundation; Research grant/Funding (institution): Boehringer; Research grant/Funding (institution): Sysmex Europe GmbH; Research grant/Funding (institution): Medica Scientia Innovation Research; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Astellas Pharma. M. Marín-Aguilera: Travel/Accommodation/Expenses: Bristol-Myers Squibb. B. Mellado: Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Novartis; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Ipsen; Research grant/Funding (institution): Bayer. All other authors have declared no conflicts of interest.