Abstract P3-13-05: Evaluating efficacy of de-escalated bisphosphonate therapy in metastatic breast cancer patients at low-risk of skeletal related events. TRIUMPH: A pragmatic multicentre trial.
Authors: N Bouganim, L Vandermeer, I Kuchuk, S Dent, S Hopkins, X Song, D Robbins, P Spencer, S Mazzarello, JF Hilton, E Amir, G Dranitsaris, C Addison, R Mallick, MJ Clemons
Journal: Cancer Research (2012)

Abstract Background: Optimal bisphosphonate (BP) dosing intervals for breast cancer patients (pts) with bone metastases (BM) remain unknown. BP are usually prescribed q3-4 wk regardless of individual pt risk for skeletal related events (SREs). Recent evidence (Amadori J Clin Oncol, 2012 suppl; abstr 9005) shows that q12 wk BP is as effective as q4 wk in pts previously treated with &amp;gt;9 cycles of q4 wk therapy. Hence, further evaluation of modified BP dosing strategies is warranted. The objective of the current study was to show in women with biochemically defined low-risk bone disease that IV BP use every q12 wk for 1 year is sufficient to maintain stability of the bone turnover [measured by serum c-telopeptide (CTx) or bone specific alkaline phosphatase (BSAP)]. Methods: Eligible pts with BM, who had received &amp;gt;3 months of q3-4 wk IV BP and no systemic treatment change within 4 wks of study entry were enrolled. Low risk was defined as serum CTx &amp;lt;600 ng/L. Biochemical failure was defined as CTx levels &amp;gt;600 ng/L at baseline, weeks 6, 12, 24, 36 or 48. Evaluation of palliative benefit of 12-wk IV BP therapy was measured by SREs, analgesic use, and self-reported pain (BPI and FACT-BP). Results: Between Oct. 2010-Sept. 2011, 85 pts consented to screening, with 13 found ineligible. In the 71 accrued pts baseline characteristics were: mean age 60 (SD 13), median time from breast cancer diagnosis to development of bone metastases 4 months (IQR 82), median duration of prior BP therapy 14 months (IQR 19), and mean number of SREs/yr prior to entering study 0.35 (SD 0.76). Baseline median CTx was 120 ng/L (IQR 240) and BSAP 9.2 IU/L (IQR 3). To date: 26/71 pts (36%) remain on study. Reasons for coming off study include; study completion (18), elevation of CTx &amp;gt;600ng/L (10), or on study SRE (3). An elevation of CTx between baseline and wk 6 was significantly associated with coming off study early (p = 0.008). For pts who had had an SRE before study entry the odds ratios for coming off study early due to an on study SRE or elevated CTx was 1.005 (CI 1.002–1.009; p = 0.007) and for coming off early for an SRE was 0.0245 (CI 0.061–0.094; p = 0.046) respectively. Of the 8/13 pts who were ineligible due to baseline CTx &amp;gt;600ng/L, 6 had an SRE within 1 year of screening. Conclusion: De-escalating BP therapy to 12 weekly in low risk pts has advantages for both the pt and the health care system. Individual risk of SREs is highly variable, however baseline serum CTx levels &amp;lt;600 ng/L is associated with a low risk of subsequent SREs. While larger trials are required to assess whether increasing CTx with de-escalated therapy will lead to higher rates of SREs or not (Coleman et al. J Clin Oncol 2012 suppl; abstr 511). However, the results of this study and Amadori et al. would suggest that de-escalated BP treatment will likely become a new standard of care after a limited period of q 4wk treatment. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-13-05.