Denosumab Versus Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma: An International, Double-Blind, Randomized Controlled Phase 3 Study-Asian Subgroup Analysis
Journal
Advances in Therapy
Journal Volume
37
Journal Issue
7
Pages
3404-3416
Date Issued
2020
Author(s)
Yoon S.-S.
Shimizu K.
Chng W.J.
Chang C.-S.
Wong R.S.-M.
Gao S.
Wang Y.
Gordon S.W.
Glennane A.
Min C.-K.
Abstract
Introduction: The primary analysis of a global phase?3 study that evaluated the efficacy and safety of denosumab versus zoledronic acid for preventing skeletal-related events (SREs) in adults with newly diagnosed multiple myeloma (MM) indicated that denosumab was noninferior to zoledronic acid for time to first on-study SREs. Here we present a subgroup analysis to evaluate efficacy and safety in Asian patients. Methods: Patients were randomized 1:1 to receive denosumab 120?mg subcutaneously or zoledronic acid intravenously 4?mg every 4?weeks in a double-blind, double-dummy fashion. All patients received standard-of-care first-line antimyeloma treatment. Each patient received either study drug until an estimated 676 patients experienced at least one on-study SRE and the primary efficacy and safety analyses were completed. Results: Of 1718 total enrolled patients, 196 Asian patients (denosumab, n = 103; zoledronic acid, n = 93) were included in this subgroup analysis. Fewer patients in the denosumab group developed first on-study SRE compared with the zoledronic acid group; the crude incidence of SREs at the primary analysis cutoff was 38.8% and 50.5%, respectively (HR [95% CI], 0.77 [0.48–1.26]). All 194 patients receiving at least one dose of study drug experienced at least one treatment-emergent AE. The most common AEs reported in either group (denosumab, zoledronic acid) were diarrhea (51.0%, 51.1%), nausea (42.2%, 46.7%), and pyrexia (38.2%, 41.3%). Treatment-emergent renal toxicity occurred in 9/102 (8.8%) and 20/92 (21.7%) patients, respectively. Similar rates of positively adjudicated osteonecrosis of the jaw (7 [6.9%] vs 5 [5.4%]) and treatment-emergent hypocalcemia (19 [18.6%] vs 17 [18.5%]) were reported in the denosumab and zoledronic acid groups, respectively. Conclusion: Efficacy and safety outcomes from this Asian subgroup were comparable to those of the full study population. Overall, this analysis supports denosumab as an additional treatment option for standard of care for Asian patients with newly diagnosed MM with lytic bone lesions. Clinical Trial Registration: ClinicalTrials.gov NCT01345019. ? 2020, The Author(s).
Subjects
Asian patients; Denosumab; Multiple myeloma; Skeletal-related event; Zoledronic acid
SDGs
Other Subjects
calcium; denosumab; placebo; vitamin D; zoledronic acid; bone density conservation agent; denosumab; zoledronic acid; acute kidney failure; adult; anemia; Article; Asian; autologous stem cell transplantation; backache; bone disease; cancer diagnosis; cancer incidence; cancer radiotherapy; cancer staging; constipation; controlled study; coughing; decreased appetite; diarrhea; double blind procedure; drug efficacy; drug safety; drug tolerability; female; fever; health care quality; herpes zoster; human; hypocalcemia; hypokalemia; insomnia; jaw osteonecrosis; major clinical study; male; middle aged; multicenter study; multiple myeloma; nausea; neutropenia; pathologic fracture; peripheral neuropathy; phase 3 clinical trial; progression free survival; randomized controlled trial; rash; spinal cord compression; thrombocytopenia; upper respiratory tract infection; vitamin supplementation; vomiting; aged; Asian continental ancestry group; bone tumor; clinical trial; comparative study; complication; multiple myeloma; treatment outcome; very elderly; Adult; Aged; Aged, 80 and over; Asian Continental Ancestry Group; Bone Density Conservation Agents; Bone Neoplasms; Denosumab; Double-Blind Method; Female; Humans; Male; Middle Aged; Multiple Myeloma; Treatment Outcome; Zoledronic Acid
Publisher
Adis
Type
journal article