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Extended Efficacy and Safety of Denosumab in Breast Cancer Patients with Bone Metastases Not Receiving Prior Bisphosphonate Therapy

Authors' Affiliations: ¹ Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; ² Medical University of Vienna, Vienna, Austria; ³ Hospital General de Mexico and ⁴ Hospital Juarez de Mexico, Mexico City, Mexico; ⁵ Clinique Victor Hugo, Le Mans, France; ⁶ Institut J. Bordet & CHU Brugmann (U.L.B.), Brussels, Belgium; ⁷ Western Hospital, Footscray, Australia; ⁸ Università Politecnica delle Marche, Ancona, Italy; ⁹ Hospital Clínic i Provincial de Barcelona, Barcelona, Spain; ¹⁰ Cross Cancer Institute, Edmonton, Alberta, Canada; ¹¹ Weston Park Hospital, Sheffield, United Kingdom; ¹² Tom Baker Cancer Centre, Calgary, Alberta, Canada; ¹³ Amgen, Inc., San Francisco, California; and ¹⁴ Amgen, Inc., Thousand Oaks, California

Requests for reprints: Allan Lipton, Milton S. Hershey Medical Center Oncology, 500 University Drive, Hershey, PA 17033-0850. Phone: 717-531-8677; Fax: 717-531-5076; E-mail: alipton{at}psu.edu.

Purpose: Denosumab, a fully human monoclonal antibody to RANKL, suppresses bone resorption. This study evaluated the effects of denosumab in i.v. bisphosphonate (IV BP)–naïve patients with breast cancer-related bone metastases.

Experimental Design: Eligible women (n = 255), stratified by type of antineoplastic therapy, were randomized to 1 of 5 blinded denosumab cohorts or an open-label IV BP cohort. Denosumab was administered s.c. every 4 weeks (30, 120, or 180 mg) or every 12 weeks (60 or 180 mg) through 21 weeks. Final efficacy results for up to 25 weeks are reported, including percentage change from baseline in urine N-telopeptide corrected for creatinine (uNTx/Cr) and incidence of skeletal-related events (SRE). Safety results are reported through the end of follow-up (up to 57 weeks).

Results: At week 13 and 25, the median percent changes in uNTx/creatinine (Cr) among patients with measurable uNTx were –73% and –75% for the pooled denosumab groups and –79% and –71% for the IV BP group. Among patients with 1 postbaseline measurement of uNTx at week 25, 52% (109 of 208) of denosumab-treated patients and 46% (19 of 41) of IV BP–treated patients achieved >65% uNTx/Cr reduction. On-study SREs occurred in 12% (26 of 211) of denosumab-treated patients and 16% (7 of 43) of IV BP–treated patients. Overall rates of adverse events were 95% in denosumab and IV BP groups. No denosumab-related serious or fatal adverse events occurred.

Conclusions: In IV BP–naïve breast cancer patients with bone metastases, denosumab suppresses bone turnover and seems to reduce SRE risk similarly to IV BPs, with a safety profile consistent with an advanced cancer population receiving systemic therapy.

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				S. Vignot and D. Khayat A Step in the Journey of Denosumab From Bone-Targeted Therapy to Seed- and Soil-Targeted Therapy J. Clin. Oncol., April 1, 2009; 27(10): 1534 - 1536. [Full Text] [PDF]