Denosumab for the treatment of bone metastases in breast cancer: evidence and opinion

Abstract

Abstract:Introduction: Denosumab, a fully human monoclonal antibody, targets the receptor activator of nuclear factor-kappaB (RANK) ligand, a protein essential for osteoclast differentiation, activity and survival. Loss of osteoclasts from the bone surface reduces bone turnover and bone loss in malignant and benign diseases. In breast cancer, bone metastases are frequently observed; cancer treatment-induced bone loss (CTIBL) may result as a consequence of endocrine treatment or chemotherapy. Furthermore, preclinical studies suggest a direct role of the RANK/RANK-ligand pathway in breast tumorigenesis. This paper reviews preclinical and clinical data on denosumab in breast cancer. Materials and methods: Studies were identified through the Medline database. Key search terms included: AMG-162, bisphosphonates, denosumab, RANK-ligand and zoledronic acid. Information available in abstract form only was retrieved from major oncology meetings, such as the American Society of Clinical Oncology (ASCO) annual meeting, ASCO breast meeting, European Cancer Organization, European Society of Medical Oncology and the San Antonio Breast Cancer Symposium. Results: Denosumab was consistently well tolerated throughout clinical trials, although the observed incidence of osteonecrosis of the jaw was comparable to that with bisphosphonates. Efficacy as determined by a reduction of skeletal-related events was at least equal to zoledronic acid, and superior in one phase III study conducted in patients with metastatic breast cancer. Clinical trials investigating the role of denosumab for the prevention of CTIBL and breast cancer recurrences are currently ongoing. Conclusion: In conclusion, denosumab appears to be an effective and safe treatment option in patients with bone metastases from breast cancer with the potential of also preventing CTIBL.

MAPK11 in breast cancer cells enhances osteoclastogenesis and bone resorption

“…[23] However, zoledronic acid’s potential as a standard of care against bone destruction is not yet fully supported, because it still offers only moderate benefits in the patients. [24] Development of more effective therapies is important for those patients with osteolytic bone destruction.…”

The RANKL/RANK system as a therapeutic target for bone invasion by oral squamous cell carcinoma

“…In the case of mandibular bone invasion, it is possible to treat the cancer with OPG locally because oral SCC cells invade from cortical bone, and the tumor and defect area are at the surface of the body. However, recent reports showed that the observed incidence of osteonecrosis of the jaw was comparable to that with bisphosphonates (52,53). Therefore, it is important to carefully consider the dosage and schedule of administration to avoid any side-effects of local injection of OPG or denosumab before the realization of the clinical application.…”

Efficacy and Safety of Denosumab for the Treatment of Bone Metastases in Patients with Advanced Cancer

“…In addition, jaw osteonecrosis developed in 2.0% of the patients in the denosumab group and 1.4% in the zoledronic acid group, with no significant difference between the groups (P ¼ 0.39). Denosumab showed better outcomes with respect to the delayed onset of SREs and the inhibitory effect on the onset of SREs than zoledronic acid, suggesting that denosumab was well tolerated by the majority of patients (Table 1) (19).…”