Number Of Skeletal-related Events Research Articles

Cost-effectiveness of oral ibandronate versus IV zoledronic acid or IV pamidronate for bone metastases in patients receiving oral hormonal therapy for breast cancer in the United Kingdom

Oral ibandronate is a single-nitrogen bisphosphonate whose efficacy is similar to that of IV ibandronate for the treatment of bone metastases. The aim of this study was to compare the cost-effectiveness of oral ibandronate with zoledronic acid and generic pamidronate (both administered by IV) for the treatment of bone metastases in patients with breast cancer receiving oral hormonal therapy in the United Kingdom. A global economic model was adapted to the UK National Health Service. Patients were assumed to receive oral hormonal therapy for 50% of their projected 14.3-month survival. The primary outcome was incremental cost per quality-adjusted life-year (QALY). Bisphosphonate efficacy data for relative risk reduction of skeletal-related events (SREs) were obtained from clinical trials. Resource use data and costs associated with IV bisphosphonate infusions were derived from published studies and a unit cost database; monthly drug acquisition costs were obtained from the British National Formulary. Utility scores were applied to time with or without an SRE to adjust survival for quality of life. Therefore, differences in QALYs were driven by utility weights rather than survival time. Model design and inputs were validated through expert UK clinician review. The absence of comparative efficacy and safety data from clinical trials for the different bisphosphonates was a model limitation that we addressed by supporting our assumptions with UK expert clinician opinion and with expert clinician opinion outside of the United Kingdom, and by conducting sensitivity analyses. The projected total cost per patient was pound307 less with oral ibandronate compared with zoledronic acid, and pound158 less compared with the use of generic pamidronate (due to a reduction in staff time for infusions, avoidance of renal safety monitoring visits, and, in the case of IV generic pamidronate, a reduction in the number of SREs). Oral ibandronate was estimated to lead to a gain of 0.02 QALY, making it the economically dominant treatment option. In this study, we found that oral ibandronate was cost-effective for the management of bone metastases from breast cancer among patients receiving oral hormonal therapy in the United Kingdom. Oral ibandronate provided effective SRE and bone-pain management while avoiding resource use and costs associated with regular IV bisphosphonate infusions. Due to uncertainty surrounding the model assumptions, it would be valuable to repeat the analyses using data from comparative bisphosphonate trials, once they become available.

Bone resorption predicts for skeletal complications in metastatic bone disease

Relationships between the rate of bone resorption (measured by urinary N-telopeptide (Ntx) excretion) and a range of skeletal complications have been evaluated in patients with metastatic bone disease. A total of 121 patients had monthly measurements of Ntx during treatment with bisphosphonates. All skeletal-related events, plus hospital admissions for bone pain and death during the period of observation, were recorded. Data were available for 121 patients over the first 3-month period of monitoring (0–3 months) and 95 patients over the second 3-month period (4–6 months). N-telopeptide levels were correlated with the number of skeletal-related events and/or death (r=0.62, P<0.001 for 0–3 months and r=0.46, P<0.001 for 4–6 months, respectively). Patients with baseline Ntx values ⩾100 nmol mmol−1 creatinine (representing clearly accelerated bone resorption) were 19.48 times (95% CI 7.55, 50.22) more likely to experience a skeletal-related event/death during the first 3 months than those with Ntx <100 (P<0.001). In a multivariate logistic regression model, Ntx was highly predictive for events/death. This study is the first to indicate a strong correlation between the rate of bone resorption and the frequency of skeletal complications in metastatic bone disease. N-telopeptide appears useful in the prediction of patients most likely to experience skeletal complications and thus benefit from bisphosphonate treatment.

Therapeutic Use of Bisphosphonates in Breast Cancer

Bisphosphonates are synthetic derivatives of phosphonate, a normal constituent of bone. These agents are potent inhibitors of osteoclastic resorption, and as such are being explored for the management of various pathological conditions including osteoporosis, hypercalcemia, bone metastases and certain aspects of cancer. Among the first agents to be developed in the class, clodronic acid has shown conflicting results with respect to its ability to reduce osseous metastases, while pamidronic acid reduced hypercalcemia effectively compared with placebo in patients with breast cancer and multiple myeloma. Recent exploratory studies have shown that the novel bisphosphonate zoledronic acid reduces hypercalcemia more effectively than pamidronic acid in patients with various malignancies. In a recent phase III trial designed to show equivalence, zoledronic acid was as effective as pamidronic acid in the number of skeletal-related events arising over a predefined period of time. Furthermore, a trend in radiation therapy delay was observed in the zoledronic acid group. Zoledronic acid appears to be an effective agent in reducing the complications from bone involvement in cancer patients and it has shown efficacy in the prevention of osteoporosis in healthy postmenopausal women. For these reasons, it is being investigated as an adjunct to adjuvant therapy for postmenopausal patients with early breast cancer treated with nonsteroidal aromatase inhibitors, because efficient and prolonged estrogen deprivation with the latter agents may result in an increased risk of bone degradation in some patients.