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Open Access 01-01-2016 | Original Article

Safety of long-term denosumab therapy: results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer

Authors: Alison T. Stopeck, Karim Fizazi, Jean-Jacques Body, Janet E. Brown, Michael Carducci, Ingo Diel, Yasuhiro Fujiwara, Miguel Martín, Alexander Paterson, Katia Tonkin, Neal Shore, Paul Sieber, Frank Kueppers, Lawrence Karsh, Denise Yardley, Huei Wang, Tapan Maniar, Jorge Arellano, Ada Braun

Published in: Supportive Care in Cancer | Issue 1/2016

Abstract

Purpose

Zoledronic acid (ZA) or denosumab treatment reduces skeletal-related events; however, the safety of prolonged therapy has not been adequately studied. Here, we describe safety results of extended denosumab therapy in patients with bone metastases from the open-label extension phase of two phase 3 trials.

Methods

Patients with metastatic breast or prostate cancer received subcutaneous denosumab 120 mg Q4W or intravenous ZA 4 mg Q4W in a double-blinded fashion. Denosumab demonstrated superior efficacy in the blinded treatment phase; thus, patients were offered open-label denosumab for up to an additional 2 years.

Results

Cumulative median (Q1, Q3) denosumab exposure was 19.1 (9.2, 32.2) months in the breast cancer trial (n = 1019) and 12.0 (5.6, 21.3) months in the prostate cancer trial (n = 942); 295 patients received denosumab for >3 years. No new safety signals were identified during the open-label phase, or among patients who switched from ZA to denosumab. During the blinded treatment phase, exposure-adjusted subject incidences of osteonecrosis of the jaw (ONJ) were 49 (1.9 %) and 31 (1.2 %) in the denosumab and ZA groups, respectively. In total, 32 (6.9 %) and 25 (5.5 %) new cases of ONJ (not adjusted for exposure) were reported for patients continuing and switching to denosumab, respectively. The incidences of hypocalcemia were 4.3 and 3.1 %, in patients continuing and switching to denosumab, respectively.

Conclusion

These results describe the safety profile of denosumab after long-term exposure, or after switching to denosumab from ZA. No new safety signals were identified. Hypocalcemia rates were similar in the blinded treatment and open-label phases. ONJ rates increased with increasing exposure to antiresorptives, consistent with previous reports.

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Title: Safety of long-term denosumab therapy: results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer
Authors: Alison T. Stopeck
Karim Fizazi
Jean-Jacques Body
Janet E. Brown
Michael Carducci
Ingo Diel
Yasuhiro Fujiwara
Miguel Martín
Alexander Paterson
Katia Tonkin
Neal Shore
Paul Sieber
Frank Kueppers
Lawrence Karsh
Denise Yardley
Huei Wang
Tapan Maniar
Jorge Arellano
Ada Braun
Publication date: 01-01-2016
Publisher: Springer Berlin Heidelberg
Published in: Supportive Care in Cancer / Issue 1/2016
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-015-2904-5

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