Abstract P2-05-13: Correlation of conventional versus experimental biomarkers of bone turnover and metastasis behaviour with skeletal related events – A biomarker analysis in conjunction with the TRIUMPH study.

Abstract BACKGROUND: Despite considerable variability in patient (pt) risk of skeletal related events (SREs) from bone metastases (BM), all pts are treated using a one size fits all approach, namely the same dose and dosing schedule (q3-4 wk) of IV bisphosphonate (BP). Identification of novel markers of individual SRE risk are thus required to better tailor treatment. TRIUMPH is an ongoing clinical trial evaluating q12 wk IV BP therapy for 1 year, following >3 months of standard q3-4 wk BP, in women with low risk bone metastases [defined by the bone resorption marker C-telopeptide (CTx) levels <600 ng/L]. This sub-study evaluated the utility of novel biomarkers in better predicting SRE risk in this low-risk cohort. METHODS: Seventy-one pts enrolled in TRIUMPH. Pt serum at baseline (69), 6 (67) and 12 (59) wks post-entry were analyzed for CTx and bone-specific alkaline phosphatase (BSAP) as per study protocol. Urine N-telopeptide (NTx) levels and serum levels of transforming growth factor-β (TGF-β), activinA, procollagen type I amino-terminal propeptide (P1NP), and bone sialoprotein (BSP) levels were also assessed by ELISA (for n=63, 63 and 57 patients at baseline, wk 6 and wk 12 respectively). Biomarker levels were correlated with pt parameters including; time to development of BM, previous SREs, and SREs post-study entry using linear regression analysis. Changes in levels of biomarkers from baseline to 6 or 12 weeks were used to calculate odds ratios of coming off study as per protocol (due to either CTx>600 ng/ml or SRE) or of SRE alone using logistic regression analysis. RESULTS: Although baseline CTx and NTx were elevated in pts who went on to develop SREs, this did not reach statistical significance. Baseline activinA trended towards total number of prior SREs (p = 0.07). Baseline TGF-β correlated with duration of BM (p = 0.004). Change in activinA (baseline to week 6) was the only biomarker that trended to predict coming off study early (p = 0.043). Results of other baseline biomarkers and changes in biomarkers from baseline to wk 12 will also be presented. CONCLUSIONS: This study further questions the role of CTx and NTx for driving treatment decisions around de-intensification of BP therapy (Coleman et al. J Clin Oncol 2012, suppl; abstr 511), and highlights the need for novel markers of SRE risk. Baseline levels of activinA was associated with the incidence of SREs in patients with BM and changes in levels from baseline to 6 weeks correlated with coming off study early. These findings warrant future studies in breast cancer pts assessing activinA as a predictor of SRE risk associated with breast cancer bone metastases. This study was supported by grants from the Ontario Institute for Cancer Research with funding from the Government of Ontario, and from the Ontario Chapter of the Canadian Breast Cancer Foundation. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-05-13.