Abstract LB-058: ABIraterone (ABI) and ENZalutamide (ENZ) induce changes in immunologic profile of patients with metastatic castration-resistant prostate cancer (mCRPC)
Authors: Salgia Meghan , Perez Marc L. , Jones Jeremy , Won Hae Jung , Poroyko Valeriy , Twardowski Przemyslaw , Kortylewski Marcin , Pal Sumanta K. 
Published: July 2017

Background: ABIraterone (ABI) is a CYP17-lyase inhibitor, while ENZalutimide (ENZ) is an androgen receptor (AR) antagonist that inhibits nuclear translocation. Changes in serum cytokines have been noted in patients (pts) receiving docetaxel for metastatic castration-resistant prostate cancer (mCPRC) therapy (Mahon KL et al Br J Cancer 2015). We postulate that ABI and ENZ may also have a complex effect on cytokine profile.

Methods: In a prospective trial in mCPRC pts, ABI or ENZ was given according to physician preference. Blood was drawn at baseline, 4 weeks, 8 weeks, 12 weeks and at the time of progressive disease (PD). Plasma was separated from patients’ blood using Vacutainer CPT tubes (BD) within 2 hours after collection by centrifuging at 1800×g for 20 min at room temperature and stored in -80°c. Plasma samples were analyzed for 30 human cytokines and chemokines using Luminex FLEXMAP 3D system. Trends in serum cytokine profile were analyzed by supervised clustering, with segregation based on radiographic progression-free survival (rPFS) according to Prostate Cancer Working Group 3 (PCWG3) criteria.

Results: From May 2013 to June 2016, 33 pts were enrolled with a median age of 67. 13 and 20 pts received ABI and ENZ, respectively. Of these, 13 pts had received prior treatment with the opposing agent (e.g., ABI→ENZ, or ENZ→ABI). Prior docetaxel was rendered in 4 pts. 16 pts had rPFS &lt; 6 mos, while 17 pts had rPFS ≥ 6 mos. Using supervised clustering, higher levels of GM-CSF (P=0.008) and IL-10 (P=0.008) were noted at 8 weeks in pts with rPFS ≥ 6 mos, while lower levels of IL-17 (P=0.008) and VEGF (P=0.001) were observed in this cohort. Across the entire cohort, a trend was noted with sequential decline in HGF from baseline to 4 and 8 weeks, but a pronounced rise was observed at the time of progression (P&lt;0.05 for comparison of progression to baseline and 4 weeks).

Conclusions: Our study suggests HGF as a mediator of ABI/ENZ resistance, supporting the well-established role of the HGF/MET signaling axis in prostate cancer pathogenesis. After initiation of therapy, lower levels of proinflammatory and proangiogenic mediators such as IL-17 and VEGF, respectively, are associated with protracted response to ABI and ENZ. These results may inform combination trials in mCRPC incorporating checkpoint inhibitors or other immune modulators.

Note: This abstract was not presented at the meeting.

Citation Format: Meghan Salgia, Marc L. Perez, Jeremy Jones, Hae Jung Won, Valeriy Poroyko, Przemyslaw Twardowski, Marcin Kortylewski, Sumanta K. Pal. ABIraterone (ABI) and ENZalutamide (ENZ) induce changes in immunologic profile of patients with metastatic castration-resistant prostate cancer (mCRPC) [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 LB-058. doi:10.1158/1538-7445.AM2017-LB-058