Abstract 2777: TMPRSS2-ERG predictive value for taxanes resistance according to prior second-line hormonal manipulations in metastatic castration resistant prostate cancer

Background: TMPRSS2-ERG is a genetic alteration specific of prostate cancer, present in primary tumors and maintained under castration resistant prostate cancer (CRPC) progression. It results in androgen-driven overexpression of ERG, which is involved in resistance to taxanes in preclinical models. In prior work, we found that TMPRSS2-ERG expression in blood correlated with docetaxel resistance in metastatic CPRC. Here, we investigated if TMPRSS2-ERG expression in primary tumors predicts taxanes resistance in CPRC and the potential impact of prior second-line hormonal manipulations with abiraterone (A) or enzalutamide (E). Methods: Patients with metastatic CRPC treated with taxanes were included. Formalin-fixed paraffin-embedded (FFPE) tumors and peripheral blood mononuclear cells (PBMCs) fraction were tested for TMPRSS2-ERG by RT-qPCR. FFPE from hormone-sensitive disease (primary diagnosis) were retrospectively obtained. PBMCs were prospectively collected prior taxane initiation. TMPRSS2-ERG expression was tested by RT-qPCR. TMPRSS2-ERG detection was correlated with taxane response and clinical outcome. Results: A total of 84 tumor samples from 74 patients were included: 65 (87.3%) treated with docetaxel, 19 (25.7%) with cabazitaxel and 10 (13.5%) with both. Forty-six tumor samples (54.7%) were TMPRSS2-ERG+ and 38 (45.2%) TMPRSS2-ERG-. Overall, no correlation between tumor TMPRSS2-ERG expression and taxanes response or clinical outcome was observed. In 42 (50%) samples matched tumor and PBMC samples were available at the time of this analysis: 23 (54.7%) had detectable TMPRSS2-ERG on tissue and 11 (26.2%) on PBMCs fraction. In 27 patients, taxanes were administered as a first-line therapy and in 15 after A or E progression. TMPRSS2-ERG was detected in PBMC from 8 (29.6%) and 3 (20%) patients without or with prior A or E. In patients without prior A or E, TMPRSS2-ERG expression in primary tumors predicted a lower median PSA-PFS (5.5 vs 10.1 months for TMPRSS2-ERG+ vs -, respectively; p Conclusions: The role of TMPRSS2-ERG in taxane resistance may be different according to prior exposure to second-line hormone-therapy in CRPC. Prior androgen receptor inhibition may result in TMPRSS2-ERG downregulation and/or activation of alternative mechanisms of resistance. Further data according to this hypothesis will be presented. Citation Format: Mercedes Marin-Aguilera, Oscar Reig, Natalia Jimenez, Ivan Victoria, Lydia Gaba, Sandra Lopez, Javier Prato, Maria Veronica Pereira, Teresa Vilella, Montserrat Domenech, Josep Badal, Albert Font, Juan Jose Garcia-Mosquera, Olatz Etxaniz, Cristina Carrato, Cristina Suarez, Joan Carles, Fabriccio Racc, Pedro Luis Fernandez, Aleix Prat, Begona Mellado. TMPRSS2-ERG predictive value for taxanes resistance according to prior second-line hormonal manipulations in metastatic castration resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2777. doi:10.1158/1538-7445.AM2017-2777