Denosumab is fully human monoclonal antibody that specifically binds and inactivates receptor activator of NF-kB ligand (RANKL), an important ligand that regulates bone remodeling. In this review, we aimed to show the clinical data of denosumab treatment and discuss its advantages for the management of patients with solid tumors and bone-metastasis.
Denosumab showed positive results in clinical studies of solid tumors with bone-metastasis. PubMed database and ASCO Symposium Meeting abstracts were searched until August 2015 by using the terms 'denosumab', 'RANKL inhibitor' and 'bone metastasis'. The last search was on August 21, 2015. All resulting studies were retrieved and were also checked for related publications. Clinical trials in this review fulfilled the following two criterion: inclusion of sufficient data to allow estimation of the efficacy and safety of denosumab.
The effects of denosumab on skeletal-related events (SRE) were investigated in three large randomized trials in patients with breast cancer or prostate cancer or solid tumors except prostate cancer and breast cancer or multiple myeloma. In breast cancer and prostate cancer studies denosumab was non-inferior and also superior to zoledronic acid in terms to primary outcome time to first on-study SRE. In the third study denosumab was non-inferior to zoledronic acid but was not superior to zoledronic acid in solid tumors except breast and prostate cancer with bone metastases. In three studies median overall survival and disease progression rates were similar between zoledronic acid and denosumab. Denosumab has also been studied in bone loss associated with hormonal therapy in both breast and prostate cancer. Adjuvant denosumab significantly reduced the risk of clinical fracture risk by 50% in breast cancer patients and by 62% in non-metastatic prostate cancer patients treated with adjuvant aromatase inhibitors or androgen deprivation therapy. In addition, biochemical markers of bone turnover and fractures were significantly reduced in patients under denosumab treatment.
The promising outcomes in the initial trials with denosumab have shown clinical activity and favorable safety profile in patients with solid tumors and bone metastasis. Denosumab significantly reduced treatment-related osteoporosis associated with breast and prostate cancer and was superior to zoledronic acid in prevention or delaying of SRE.
Current medical research and opinion. 2015 Oct 09 [Epub ahead of print]
Gözde Gül, Mehmet A N Sendur, Sercan Aksoy, Ali R Sever, Kadri Altundag
a a Hacettepe University Cancer Institute, Department of Medical Oncology , Ankara , Turkey. , b b Yıldırım Beyazıt University Faculty of Medicine, Department of Medical Oncology , Ankara , Turkey. , a a Hacettepe University Cancer Institute, Department of Medical Oncology , Ankara , Turkey. , c c Hacettepe University School of Medicine, Department of Radiology , Ankara , Turkey. , d d Hacettepe University Cancer Institute, Hacettepe University Oncology Hospital , Sihhiye , Ankara , Turkey.