1583P - Prospective study of treatment pattern, effectiveness, and safety of zoledronic acid (ZOL) therapy beyond 24 months in patients (pts) with multiple...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Supportive Care
Plasma Cell Dyscrasias
Presenter Tim van den Wyngaert
Authors T. van den Wyngaert1, M. Delforge2, C. Doyen3, L. Duck4, K. Wouters5, I. Delabaye6, C. Wouters6, H. Wildiers7, . On Behalf Of Bsmo/bhs And Lotuz Investigators.1
  • 1Nuclear Medicine, Antwerp University Hospital, 2650 - Edegem/BE
  • 2Hematology, University Hospitals Leuven, Leuven/BE
  • 3Hematology, Cliniques Universitaires UCL, Godinne/BE
  • 4Clinique St. Pierre, BE-1340 - Ottignies/BE
  • 5Biostatistics, Antwerp University Hospital, Edegem/BE
  • 6Novartis Oncology, Novartis Pharmaceuticals, Vilvoorde/BE
  • 7General Medical Oncology, University Hospitals Leuven, Leuven/BE



Trial data documenting ZOL treatment is currently limited to approximately 2 years of therapy.


Pts with MM or STM and with at least 24 months of regular q3-4w ZOL therapy were followed for 18 months. ZOL could be continued, interrupted or stopped at the discretion of the treating physician. End-points included ZOL exposure, incidence of skeletal related events (SRE), and safety.


In all, 298 evaluable pts were enrolled (female n = 201; median age 66y). Pts had MM (31.2%), breast- (52.7%), prostate cancer (11.7%), or another solid tumor (4.4%). The mean continuation rate of ZOL was 90.6%, even though only 28.0% of pts who completed follow-up (n = 218) received uninterrupted per-label ZOL therapy. Exposure to ZOL decreased steadily with time in all pts, but was on average lower (50.0% vs 67.6%; p < 0.001) and with higher discontinuation rates (IRR 1.95; p = 0.002) in MM compared to STM pts. ZOL infusions were extended beyond 15 minutes in 39.5%, and the treatment interval exceeded 4 weeks in 29.3% of pts. ZOL continued to suppress the rate of SREs similarly during the 18 months study period (0.14 per person-year) as compared to the 18 months before inclusion (0.13 per person-year; p = 0.9). At 18 months, 82.7% (95% CI 77.4 – 87.0%) of pts were SRE free. The rate of SREs was lower in MM compared to STM pts (IRR 0.48; p = 0.03). In STM pts, persistent ZOL therapy reduced the SRE risk (HR 0.42; p = 0.01) compared to interrupted treatment. Renal deterioration occurred in 11 pts (3.7%), with a higher risk when ZOL dose was not adjusted for renal function (HR 3.96; p = 0.03), as observed in 12.5% of pts. Symptomatic hypocalcemia was not reported, although adherence to supplemental calcium and vitamin D was only 18.5%. Acute phase reactions were infrequent (6.4%) and ONJ developed in 6.0% of pts. Invasive dental procedures or trauma were associated with increased ONJ risk (HR 4.67; p = 0.002), with a 20% risk of ONJ after any of these events.


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 interrupting ZOL therapy in pts with STM was associated with a higher SRE risk. The long-term safety profile of ZOL was favorable, but adequate prevention strategies for ONJ remain important.


T. van den Wyngaert: Advisory board Novartis,

M. Delforge: Lecture fees from Novartis,

I. Delabaye: Employee of Novartis Pharmaceuticals,

C. Wouters: Employee of Novartis Pharmaceuticals.

All other authors have declared no conflicts of interest.