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202 Background: Enzalutamide improve overall survival (OS) in patients with metastatic castrate resistant prostate cancer (mCRPC) patients following docetaxel treatment. Optimal sequencing and possible cross-resistance for novel mCRPC therapeutics is less understood. In this study we report biochemical response and OS after enzalutamide treatment in post-chemo mCRPC patients following progression on post-chemo abiraterone treatment. Methods: Twenty-four post-chemotherapy and post-abiraterone mCRPC patients with progressive disease received enzalutamide 160 mg/daily in a Danish compassionate-use program sponsored by Astellas Pharma A/S. Best PSA and alkaline phosphatase response was recorded. Fischer’s exact test, Mann-Whitney U test and linear regression model was used to test for differences in PSA response. OS was calculated from initiation of enzalutamide treatment. Results: Minimum follow-up was three months. The best median PSA response was -22% (-76% to 76%). Forty-six percent of patients had a greater than 30% decrease in PSA. The PSA response to enzalutamide did not correlate to the number of prior cancer treatments (p = 0.57), time from diagnosis to CRPC (p = 0.11), or prior response to docetaxel (p = 0.67). However, eight patients treated with second line cabazitaxel had an inferior PSA response to enzalutamide (p = 0.03), and there was a trend for the PSA response to abiraterone to correlate with the PSA response to the succeeding enzalutamide (B = 0.22, p = 0.05). The best median alkaline phosphatase response was 0.1% (-67% to 126%). Median OS was 4.8 months. Conclusions: Patients with post-chemotherapy, post-abiraterone mCRPC treated with enzalutamide showed less marked biochemical response to therapy compared to the results from the AFFIRM study where post-chemo abiraterone was not used. Whether this is an effect of cross-resistance or a result of the natural history of the disease needs further elaboration.

226 Background: The automated BSI (auto-BSI) is a computerized means of quantitatively expressing tumor burden in bone. Following the analytical validation of auto-BSI, we are now clinically qualifying the tool as a response biomarker in mCRPC. In the present study, we assess the association of auto-BSI and that of PSA with overall survival (OS) in mCRPC patients (pts) being treated with enzalutamide. Methods: All mCRPC pts who initiated enzalutamide treatment at Skåne Hospital, Sweden and at Rigshospitalet, Denmark, with a minimum of one year follow-up, were eligible for the study. Eligible mCRPC pts with baseline (BL) bone scan available before starting enzalutamide were enrolled in the study. PSA, hemoglobin (Hgb) and alkaline phosphatase (ALP) were obtained at BL. Treatment follow-up PSA and auto-BSI were obtained at week-12. auto-BSI was obtained using the analytically validated EXIN boneBSIversion 2.0. Cox regression and concordance index (c-index) were used to evaluate the association with OS. Results: 80 mCRPC pts with BL bone scans were enrolled in the study. Treatment follow-up bone scans were available from 62 pts. Univariate analysis demonstrated that auto-BSI, PSA, ALP and Hgb at BL were associated with OS (p < 0.0001). In the multivariate analysis, only auto-BSI and HgB were significantly associated with OS. The auto-BSI showed the highest c-index in prediction of OS (c-index 0.72, SE 0.03). Adding auto-BSI to the BL covariate model significantly improved the discrimination from c-index 0.67 to 0.72 (p < 0.05). At treatment follow-up, the univariate analysis of the change in auto-BSI and the percent change in PSA were strongly associated with OS with c-index 0.76 and 0.72 (SE 0.05), respectively. In bivariate analysis, the change in auto-BSI remained strongly associated with OS (p < 0.0001) whereas the percent change in PSA appeared to be less so (p = 0.07). Conclusions: Auto-BSI and its change demonstrated an independent and a strong association with OS in mCRPC pts being treated with enzalutamide. The study serve as a foundation for prospective validation of auto-BSI as an imaging biomarker indicative of efficacy to enzalutamide.

Prostate needle biopsy cores from 249 participants in the PICTURE study (patients with a previous biopsy who underwent mpMRI followed by 5 mm transperineal mapping biopsies) were obtained. Malignant core segments (from the area with the highest Gleason score and cancer core length) as well as adjacent benign core segments were divided according to pathology on H&E and then embedded vertically into a TMA block. TMA slides were immunohistochemically stained against known prostate cancer biomarkers (PSA, PSMA, AMACR, p63, MSMB) and h-scored. Paired h-score data (i.e. from malignant and adjacent benign tissue) were compared. Visualization of h-scores against mpMRI Likert scores was also performed.RESULTS: A total of 136 pairs of malignant-benign core segments were stained. There was a statistically significant difference in hscore expression between malignant and paired benign tissue for all biomarkers, but particularly for AMACR, p63 and MSMB (Wilcoxon paired signed-rank test, p<0.001). There was no obvious correlation between IHC h-score and MRI Likert score.CONCLUSIONS: PSA, PSMA, AMACR, p63 and MSMB IHC hscores in mpMRI-characterized, malignant prostate tissue significantly differ from h-scores in surrounding benign areas, despite their proximity. This suggests a distinct expression pattern that is detectable on TMAs derived from prostate needle biopsies.