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Zoledronic Acid Shows Significant Antitumor Activity in Multiple Myeloma
June 6, 2010—During the 46th Oncology Annual Meeting in Chicago, Illinois, Gareth Morgan, MD, PhD (University of Chicago, Chicago, Illinois), presented results from the MRC (Medical Research Council) Myeloma IX Study, comparing the effects of zoledronic acid versus clodronate in combination with standard antimyeloma therapy in patients with newly diagnosed multiple myeloma.
Bisphosphonates have long been standard of care for patients with bone lesions from multiple myeloma based on evidence that they significantly reduce bone pain and skeletal complications such as pathologic fractures. But do they also have meaningful antitumor effects in patients with bone metastases from solid tumors or bone lesions from multiple myeloma? Until recently, this has been a highly controversial question. The ABCSG-12 study in early breast cancer provided the first clinical evidence that addition of zoledronic acid to standard endocrine therapy can significantly improve disease-free survival compared with endocrine therapy alone (Gnant M, et al. N Engl J Med. 2009;360(7):679-691). In an effort to further define the antitumor potential of zoledronic acid, the MRC Myeloma IX Study investigated the effects of zoledronic acid (4 mg IV q 3-4 weeks) versus oral clodronate (1600 mg/day) in combination with standard antimyeloma therapy in 1970 patients with newly diagnosed multiple myeloma. Clinical endpoints included overall (OS), progression-free survival (PFS), and skeletal-related events (SREs). At a median follow-up of approximately 4 years, zoledronic acid not only reduced the percentage of patients with an SRE compared to clodronate (27% versus 35%; P = .0004) but also significantly improved both OS and PFS. Median OS was improved by >5 months (50.0 months versus 44.5 months; P = .0118) and median PFS was improved by 2 months (19.5 versus 17.5 months; P = .0179). Importantly, the OS benefit associated with zoledronic acid was maintained after adjustment in a Cox model analysis for the potential effects of SREs on survival. The authors reported that both bisphosphonates were generally well-tolerated. Decreased renal function was similar in both treatment groups. Osteonecrosis of the jaw occurred in 3.6% of patients treated with zoledronic acid and 0.3% of patients treated with oral clodronate. These rates are similar to those seen previously in this patient population. Zoledronic acid added to standard anti-myeloma therapy was generally well tolerated and resulted in an overall survival benefit, which was independent of SRE reduction. These results further support the anticancer activity of zoledronic acid and provide evidence suggesting integration of zoledronic acid early during treatment of multiple myeloma.
J Clin Oncol. 2010;28(7s): Abstract 8021.
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