Delaying skeletal-related events in a randomized phase 3 study of denosumab
versus zoledronic acid in patients with advanced cancer: an analysis of data from
patients with solid tumors.
Author(s): Henry D(1), Vadhan-Raj S, Hirsh V, von Moos R, Hungria V, Costa L, Woll PJ,
Scagliotti G, Smith G, Feng A, Jun S, Dansey R, Yeh H.
Affiliation(s): Author information:
(1)Joan Karnell Cancer Center, Pennsylvania Hospital, 230 W Washington Square,
Philadelphia, PA, 19106, USA, davidhenry@pennoncology.com.
Publication date & source: 2014, Support Care Cancer. , 22(3):679-87
PURPOSE: Bone complications of metastatic disease, including skeletal-related
events (SREs), impair patients' functioning and quality of life. In a randomized,
phase 3 trial of 1,776 patients with metastases from solid tumors (except breast
or prostate) or multiple myeloma, denosumab was non-inferior to zoledronic acid
(ZA) in delaying or preventing SREs. This ad hoc analysis reports outcomes in the
subgroup of 1,597 patients with solid tumors, excluding patients with multiple
myeloma.
METHODS: Patients received monthly subcutaneous denosumab 120 mg or intravenous
ZA 4 mg, adjusted for creatinine clearance, with calcium and vitamin D
supplementation recommended. Endpoints included times to first on-study SRE,
first-and-subsequent SREs, and pain worsening.
RESULTS: Denosumab significantly delayed time to first on-study SRE compared with
ZA (HR, 0.81; 95 % CI, 0.68-0.96) and time to first-and-subsequent SREs (RR,
0.85; 95 % CI, 0.72-1.00). Denosumab also significantly delayed time to
development of moderate or severe pain (HR, 0.81; 95 % CI, 0.66-1.00), pain
worsening (HR, 0.83; 95 % CI, 0.71-0.97), and worsening pain interference in
patients with no/mild baseline pain (HR, 0.77; 95 % CI, 0.61-0.96). Adverse event
rates were 96 % in both groups. Grade 3 or 4 hypocalcemia, mostly without
clinical sequelae, was more frequent in denosumab-treated patients (denosumab 4
%, ZA 2 %). Osteonecrosis of the jaw occurred infrequently (denosumab 0.8 %, ZA
1.1 %).
CONCLUSIONS: Denosumab was more effective in delaying or preventing SREs in
patients with bone metastases from solid tumors and also prevented pain
progression compared to ZA in this ad hoc analysis.
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