Abstract P3-13-01: Prospective study of treatment pattern, effectiveness, and safety of zoledronic acid (ZOL) therapy beyond 24 months: subgroup analysis of patients (pts) with metastatic bone disease (MBD) from breast cancer (BC).
Authors: Van den Wyngaert T , Delforge M , Doyen C , Duck L , Wouters K , Delabaye I , Wouters C , Wildiers H 
Published: August 2014

Abstract
Background: Trial data documenting ZOL treatment in pts with MBD from BC is currently limited to approximately 2 years of therapy.
Materials and Methods: The prospective multicenter LOTUZ trial studied pts with multiple myeloma or MBD from a solid tumor (n = 298), and with at least 24 months of regular q3-4w ZOL therapy. Follow-up was 18 months and ZOL could be continued, interrupted or stopped at the discretion of the treating physician. End-points included ZOL exposure (% of expected per-label cumulative dose) and persistence (no treatment interruptions &gt; 45 days), incidence of skeletal related events (SRE), and safety. Here we present the results for the subgroup of BC pts.
Results: A total of 157 women (median age 62y; range 38 — 87y) were included in this analysis (204 person-years follow-up). The mean continuation rate of ZOL at any visit was 92.1% (95% CI 90.3 — 93.9), even though only 37.0% of pts who completed follow-up (n = 108) received uninterrupted per-label ZOL therapy. On average, exposure to ZOL decreased with 2.23% per 3 months on study (95% CI 0.93 — 3.54; p = 0.001). ZOL infusions were extended beyond 15 minutes in 36.1% (95% CI 33.7 — 38.6), and the treatment interval exceeded 4 weeks in 28.4% of pts (95% CI 19.6 — 38.6). Overall, ZOL continued to suppress the rate of SREs similarly during the 18 months study period (0.127 per person-year) as compared to the 18 months before inclusion (0.135 per person-year; p = 0.8). Radiation to bone occurred most frequently (46.2%) out of a total of 26 observed SREs. At 18 months, 83.3% (95% CI 75.6 — 88.8) of pts were SRE free. Both higher exposure to ZOL (HR 0.76 per 20% increase; 95% CI 0.62 — 0.93; p = 0.009) and persistent ZOL therapy (HR 0.26; 95% CI 0.11 — 0.60; p = 0.002) were associated with significantly lower SRE risk, compared to pts receiving lower dosed or interrupted therapy. Renal deterioration occurred in 6 pts (event rate 0.03 per person-year; 95% CI 0.01 — 0.07), with a numerically higher risk when ZOL dose was not adjusted for renal function (HR 3.54; 95% CI 0.65 — 19.4; p = 0.14), as observed in 11.5% of pts. Symptomatic hypocalcemia was not reported, even though adherence to supplemental calcium and vitamin D was only 15.9%. Acute phase reactions were infrequent (9.5%) and ONJ developed in 7 pts (4.5%). Invasive dental procedures or trauma numerically increased ONJ risk (HR 2.87; p = 0.3), with a risk of ONJ of 11.1% (95% CI 0.2 — 48.2%) after any of these events.
Conclusion: The continuation rate of ZOL beyond two years of therapy is high and ZOL demonstrated continued effectiveness in maintaining low SRE rates. Nevertheless, ZOL treatment patterns were heterogeneous and deviating from per-label ZOL therapy resulted in a higher SRE risk. The long-term safety profile of ZOL was favorable, but adequate prevention strategies for ONJ remain important.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-13-01.