David H. Henry1, Luís Costa1, François Goldwasser1, Vera Hirsh1, Vânia Hungria1, Jana Prausová1, Giorgio V. Scagliotti1, H.P. Sleeboom1, Andrew Spencer1, Saroj Vadhan‐Raj1, Roger von Moos1, Wolfgang Willenbacher1, Penella J. Woll1, Jianming Wang1, Qi Jiang1, Susie Jun1, Roger Dansey1, Howard Yeh1
1From the Joan Karnell Cancer Center, Philadelphia, PA; Hospital de Santa Maria and Instituto de Medicina Molecular, Lisboa, Portugal; Teaching Hospital Cochin, Paris, France; McGill University Health Centre, Montreal, Canada; Irmandade da Santa Casa de Misericordia de Sao Paulo, Sao Paulo, Brazil; University Hospital Motol, Prague, Czech Republic; University of Torino, Orbassano, Italy; HagaZiekenhuis-Leyenburg, Den Haag, the Netherlands; The Alfred Hospital, Melbourne, Australia; MD Anderson Cancer...
Tóm tắt
Purpose This study compared denosumab, a fully human monoclonal anti-receptor activator of nuclear factor kappa-B ligand antibody, with zoledronic acid (ZA) for delaying or preventing skeletal-related events (SRE) in patients with advanced cancer and bone metastases (excluding breast and prostate) or myeloma. Patients and Methods Eligible patients were randomly assigned in a double-blind, double-dummy design to receive monthly subcutaneous denosumab 120 mg (n = 886) or intravenous ZA 4 mg (dose adjusted for renal impairment; n = 890). Daily supplemental calcium and vitamin D were strongly recommended. The primary end point was time to first on-study SRE (pathologic fracture, radiation or surgery to bone, or spinal cord compression). Results Denosumab was noninferior to ZA in delaying time to first on-study SRE (hazard ratio, 0.84; 95% CI, 0.71 to 0.98; P = .0007). Although directionally favorable, denosumab was not statistically superior to ZA in delaying time to first on-study SRE (P = .03 unadjusted; P = .06 adjusted for multiplicity) or time to first-and-subsequent (multiple) SRE (rate ratio, 0.90; 95% CI, 0.77 to 1.04; P = .14). Overall survival and disease progression were similar between groups. Hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred at similarly low rates in both groups. Acute-phase reactions after the first dose occurred more frequently with ZA, as did renal adverse events and elevations in serum creatinine based on National Cancer Institute Common Toxicity Criteria for Adverse Events grading. Conclusion Denosumab was noninferior (trending to superiority) to ZA in preventing or delaying first on-study SRE in patients with advanced cancer metastatic to bone or myeloma. Denosumab represents a potential novel treatment option with the convenience of subcutaneous administration and no requirement for renal monitoring or dose adjustment.
