Bone Metastases in Breast Cancer

Bone Metastases in Breast Cancer

Allan Lipton
US Oncology Review 2006
Published: October 2008
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A pooled analysis of these two trials demonstrated that treatment with pamidronate resulted in statistically significant reductions in all types of skeletal complications and bone pain compared with placebo.3 In these trials, 751 patients were treated with pamidronate (90mg) or placebo every three to four weeks. After 24 months of therapy, pamidronate significantly reduced the percentage of patients who experienced at least one SRE excluding hypercalcemia (51% versus 64% for placebo; p<0.001; see Figure 2)3,6,9 and the annual incidence of SREs (2.4 versus 3.7 SREs/year for placebo; p<0.001), and significantly delayed the median time to the first SRE by more than five months (12.7 versus seven months for placebo; p<0.001). At 24 months, pamidronate also significantly reduced mean pain scores (p=0.015 versus placebo) and analgesic scores (p<0.001 versus placebo) from baseline compared with increases from baseline in the placebo group.Moreover, these trials validated the composite SRE end-point and set a new standard for clinical evaluation of bisphosphonates for the treatment of malignant bone disease.

Ibandronate
Recently, IV ibandronate was approved in Europe for the treatment of bone metastases in patients with breast cancer, on the basis of a randomized trial comparing IV ibandronate (2mg or 6mg) with placebo.11 This study defined bone events as vertebral fractures, pathologic non-vertebral fractures, and radiation or surgery to bone. In this trial involving 466 patients, IV ibandronate (6mg via one- to two-hour infusion) every three to four weeks for up to 96 weeks significantly reduced the skeletal morbidity period rate (SMPR)—defined as the number of 12-week periods with a new bone event divided by number of periods on study—compared with placebo (p=0.004) and significantly delayed the median time to first bone event (50.6 versus 33.1 weeks for placebo; p=0.018).11 In contrast, the 2mg bolus IV dose was not effective. In addition, at last evaluation, IV ibandronate (6mg) significantly reduced mean pain scores (assessed on a 5-point scale) from baseline compared with increased pain scores in both the 2mg ibandronate and placebo groups (p<0.001 versus placebo).25

Recently, studies have also demonstrated the clinical benefit of oral ibandronate in preventing skeletal complications in breast cancer patients with bone metastases. Pooled results from two randomized studies involving 564 patients demonstrated that oral ibandronate (50mg/day for 96 weeks) significantly reduced the SMPR compared with placebo (p=0.004).14

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