Association of bone scan index (BSI) with prognostic biomarkers and survival in men with metastatic castration-resistant prostate cancer (mCRPC) enrolled in a prospective randomized controlled trial of tasquinimod.

Abstract

5081 Background: Tasquinimod (T) is an oral immunomodulatory and anti-angiogenic agent currently in phase 3 testing in mCRPC. In a randomized, double-blind phase 2 multicenter study, 201 men with mCRPC who received T had improved radiographic PFS vs. placebo (P), with a more pronounced effect seen in men with bone metastases. Given the subjectivity/variability of bone scan measurements, we sought to evaluate the bone scan index (BSI), a quantitative and objective measure of BS activity, over time in this controlled clinical trial. Post-treatment BSI changes were examined given their prior association with survival. Methods: In this retrospective analysis, Exini bone™, an automated software package that generates the BSI (percent tumor involvement) from 99Tc BS, was used to calculate BSI over time from BS collected during central review in this randomized trial of T vs. P. Associations between baseline and on-treatment BSI, survival, prognostic biomarkers, and treatment effect were evaluated. Results: 108 men contributed baseline scans for BSI analysis that met quality control metrics (74 T vs. 34 P), 85 of whom (57 T vs. 28 P) had at least 1 evaluable follow-up week 12 scan. Median baseline BSI was 0.90% and after 3 months median BSI was 1.21%. In univariate analysis (n=85) baseline BSI correlated with OS (HR 1.41; p=0.01). Both baseline BSI (HR 1.62; p=0.006) and week 12 BSI change (HR 1.95; p=0.002) remained associated with OS after adjustment for bone alkaline phosphatase, PSA, pain score, hemoglobin, and treatment arm. BSI correlated with baseline PSA, LDH, bone alkaline phosphatase, and the number of bone lesions. The increase in BSI at week 12 vs. baseline was slower with T vs. placebo (0.16% vs. 0.26% increase). Conclusions: BSI and BSI changes were associated with OS in men with mCRPC in this prospective trial. BSI correlates with known biomarkers of OS, but adds independent prognostic information. While underpowered, a delay in objective radiographic bone scan progression with tasquinimod is suggested and the evaluation of BSI and BSI changes in the context of phase 3 trials of men with mCRPC is warranted. Clinical trial information: NCT00560482.