Lay Summary: Zometa has defined indications for breast cancer.
Zometa (chemical name: zoledronate) is a medication that has been found to help stop bone loss. It was initially approved in the US in 2001 for the treatment of hypercalcemia of malignancy (HCM), also known as tumor-induced hypercalcemia (TIH). It was approved in 2002 for the treatment of bone lesions in myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard cancer therapy.
The 3 largest studies ever conducted to determine the effect of IV bisphosphonate on the management of bone metastases demonstrated that zoledronic acid significantly reduces the occurrence and delays the onset of skeletal complications in patients with bone metastases secondary to a variety of solid tumors and bone lesions associated with multiple myeloma. The primary efficacy end point in all 3 trials was the percentage of patients who experienced at least 1 skeletal event, defined as a pathologic fracture, radiation therapy or surgery to bone, or spinal cord compression. HCM, another skeletal event, was included in the analysis of secondary end points: time to the first skeletal event, skeletal morbidity rate (ie, number of events per year), and a multiple event analysis of the ongoing risk of skeletal morbidity that integrated the incidence and timing of all skeletal events.
In one of these randomized, controlled, phase 3 studies, zoledronic acid was compared with pamidronate in 1648 patients with either stage IV breast cancer or Durie-Salmon stage III multiple myeloma and at least 1 bone lesion. In these patients, zoledronic acid (4 mg via 15-minute infusion) administered every 3 to 4 weeks for 12 months was as effective and well tolerated as pamidronate (90 mg via 2-hour infusion). The percentage of patients who experienced at least 1 skeletal event after 13 months was similar in both treatment groups. Zoledronic acid performed better than pamidronate in every clinical end point measured and significantly reduced the incidence of radiation to bone in the overall patient population (P = .031) and in patients with breast cancer. Patients in this trial had a median survival of > 2 years, and were therefore at chronic risk of skeletal morbidity. A sensitive multiple event analysis also showed a significant reduction in the ongoing risk of developing skeletal complications in the 1130 patients with breast cancer included in this trial.
In addition to this comparative trial, 2 randomized, placebo-controlled trials were conducted in patients with a variety of solid tumors metastatic to bone, including prostate cancer, lung cancer, and renal cell carcinoma. In 643 patients with malignant bone disease from prostate cancer that had progressed during hormone therapy, 4 mg of zoledronic acid significantly and consistently reduced skeletal morbidity over a 15-month period. Patients in this trial had a median survival of almost 2 years. Zoledronic acid significantly reduced the number of patients with a skeletal event (P = .021). A prospectively designed multiple event analysis, based on a robust statistical model, demonstrated a 36% reduction in the risk of skeletal complications for patients treated with 4 mg zoledronic acid compared with placebo (P = .004). Additionally, the pain scores for patients receiving zoledronic acid were reduced relative to those of the placebo group at every time point. This was the first randomized, placebo-controlled study to demonstrate efficacy of a bisphosphonate in men with advanced prostate cancer.
The second placebo-controlled, phase 3 trial of zoledronic acid enrolled 773 patients with bone metastases from other solid tumors (including lung, renal, and bladder cancer). Zoledronic acid delayed the time to the first skeletal complication by more than 2 months compared with placebo (P = .007) and delayed the time to the first pathologic fracture by more than 2 months (P = .031). The multiple event analysis also showed a significant 27% reduction in the overall risk of developing skeletal complications for the zoledronic acid group (P = .017). These results are impressive considering the poor prognosis for patients with bone metastases from solid tumors, who have a median survival of only approximately 6 months.
Zometa is not FDA approved for osteoporosis in breast cancer patients on aromatase inhibitors but NCCN recommends it as as 4mg twice a year.
.Efficacy of zoledronic acid and pamidronate in breast cancer patients: a comparative analysis of randomized phase III trials. Am J Clin Oncol.
2002 Dec;25(6 Suppl 1):S25-31.
Breast Cancer Disease Site Group. Warr D, Johnston M. Use of bisphosphonates in women with breast cancer [full report]. Toronto (ON): Cancer Care Ontario (CCO); 2004 Apr [online update]. 34 p. (Practice guideline report; no. 1-11). [68 references]
NCCN.ORG, Breast Cancer, 2012,
Zolendronic Acid, Prescribing Information