Biomarkers for early prognostication of outcome in patients with bone-metastatic castration-resistant prostate cancer treated with enzalutamide.

Abstract

e16507 Background: Enzalutamide (Enza) prolongs survival in men with mCRPC in pre- and post chemotherapy setting. Commonly used prostate-specific antigen (PSA) may lead to non-straightforward prognosis. This is especially true for bone mCRPC (bmCRPC) in which initial bone-flare may add to difficult decision making. During other therapies, bouncing of alkaline phosphatase (ALP-Bounce) was shown as a promising surrogate for survival outcome. The purpose of this study was to evaluate the prognostic ability of ALP-Bounce compared to standard PSA and lactate dehydrogenase (LDH) after initiation of Enza. Methods: Patients with bmCRPC were included and analyzed. PSA, LDH and ALP were monitored at 2, 4, 8 and 12 weeks under very early Enza treatment. ALP-Bounce vs. no Bounce was analyzed using Kaplan-Meier estimates and uni- and multivariate (UV/MV) cox-regression models. ALP-Bounce was defined as an increase of ALP after initiation of Enza with a subsequent, significant decline below baseline during the first 8 weeks of therapy. Results: Eighty-nine men were evaluable for analysis. The median overall survival (OS) of men with ALP-Bounce was 19 months (95% confidence interval: 7.9-30.1) compared to 12 months (7.7-16.3) for no Bounce. Analysis of progression-free survival (PFS) showed similar results with 8 (0-16.3) vs. 3 months (1.9-4.1). In UV no ALP-Bounce (Hazard Ratio (HR): 1.9 (1.1-3.3); p = 0.02), no PSA-decline ≥50% (HR: 2.3 (1.5-3.7); p < 0.01) and no LDH-Normalization (HR: 2.5 (1.6-4.1); p < 0.01) were significantly associated with worse PFS. In MV only no ALP-Bounce showed a trend towards worse PFS (HR: 2.1 (0.9-4.5); p = 0.09). In UV no LDH-normalization was a significant prognosticator of poor OS (HR: 2.6 (1.6-4.2); p < 0.01) while ALP-Bounce and PSA decline ≥50% were non-prognostic. In MV no LDH-normalization remained an independent prognosticator of poor OS (HR: 2.0 (1.1.-3.5); p = 0.02). Conclusions: ALP-Bounce and LDH-Normalization may add to identification of bmCRPC-patients with favorable prognosis during early therapy with Enza. The early occurence of ALP-Bounce might be beneficial. These results have to be validated in a prospective trial.