TY - JOUR
T1 - Safety of long-term denosumab therapy
T2 - results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer
AU - Stopeck, Alison T.
AU - Fizazi, Karim
AU - Body, Jean Jacques
AU - Brown, Janet E.
AU - Carducci, Michael
AU - Diel, Ingo
AU - Fujiwara, Yasuhiro
AU - Martín, Miguel
AU - Paterson, Alexander
AU - Tonkin, Katia
AU - Shore, Neal
AU - Sieber, Paul
AU - Kueppers, Frank
AU - Karsh, Lawrence
AU - Yardley, Denise
AU - Wang, Huei
AU - Maniar, Tapan
AU - Arellano, Jorge
AU - Braun, Ada
N1 - Publisher Copyright:
© 2015, The Author(s).
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
KW - Bone metastases
KW - Breast cancer
KW - Denosumab
KW - Osteonecrosis of the jaw
KW - Prostate cancer
KW - Zoledronic acid
UR - http://www.scopus.com/inward/record.url?scp=84949085967&partnerID=8YFLogxK
U2 - 10.1007/s00520-015-2904-5
DO - 10.1007/s00520-015-2904-5
M3 - Article
C2 - 26335402
AN - SCOPUS:84949085967
SN - 0941-4355
VL - 24
SP - 447
EP - 455
JO - Supportive Care in Cancer
JF - Supportive Care in Cancer
IS - 1
ER -