Major trial confirms value of zoledronic acid dosed every 3 months in preventing pain, SREs


An interesting paper that we managed to miss at the recent annual meeting of the American Society of Clinical Oncology (ASCO) provided the results of a large, randomized clinical trial of the use of zoledronic acid, carried out by the Cancer and Leukemia Group B cooperative trial group.

In this trial, the investigators set out to test whether giving zoledronic acid every 3 months would be just as effective (i.e., “non-inferior”) at reducing bone pain and skeletal-related events (SREs) in patients with bone metastases as giving it according to the standard recommended regimen (once a month) specified in the product’s prescribing information.

SREs were defined as any skeletal event requiring radiation therapy to bone, fractures, spinal cord compression, or surgery to bone within 24 months of initiation of the study. The study’s primary endpoint was the proportion of patients in each group who had at least one SRE; secondary endpoints included skeletal morbidity rates, performance status, pain (evaluated using the Brief Pain Inventory), and the incidences of osteonecrosis of the jaw and renal dysfunction.

Here are the study findings reported by Himelstein et al. at the ASCO meeting:

  • Between May 1, 2009 and April 13, 2012, a total of 1,822 patients at risk for SREs were enrolled and randomized to zoledronic acid either once monthly or once every 3 monthsin cluding
    • 674 men with prostate cancer
    • 833 patients with breast cancer
    • 270 patients with multiple myeloma, and
    • 45 others
  • Baseline characteristics of the two groups of patients rnadomized to the two different doses of zoledronic acid were comparable.
  • Dose delays were more common among patients treated once monthly, occurring in
    • 62 percent of patients treated once monthly
    • 37 percent of patients treated every 3 months
  • The 2-year cumulative incidences of SREs and selected toxicities are
    • Occurrence of any SRE in all patients
      • 260 in patients treated once monthly
      • 253 in patients every 3 months
      • Hazard ratio (HR) = 1.05; P = 0.60
    • Occurrence of any SRE in prostate cancer patients
      • 107 in patients treated once monthly
      • 101 in patients treated every 3 months
      • HR = 1.15; P = 0.31
  • Bone surgeries were more common among patients treated every 3 months, occurring in
    • 22 patients treated once monthly
    • 42 patients treated every 3 months
    • HR = 0.51; P =0.01
  • Osteonecrosis of the jaw was more common among patients treated once monthly, occurring in
    • 18 patients treated once monthly
    • 9 patients treated every 3 months

The authors conclude that, when zoledronic acid is administered every 3 months, it is is non-inferior to zoledornic acid administered monthly for 24 months in patients with breast cancer, prostate cancer, and multiple myeloma.

In picking this paper as one of the 10 practice-changing presentations from the annual ASCO meeting, Kirschner states that this less frequent dosing of zoledronic acid “will be less expensive and result in fewer visits for our patients and probably an improved quality of life.”

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