Adjuvant therapy with bone-targeted agents

Abstract

The use of bone-targeting agents in the adjuvant setting has focused on two main areas: prevention of chemotherapy-induced bone loss (CTIBL) and the potential antitumour effects in preventing development of metastasis. Here, we review recent advances within these two areas. Trials of oral and intravenous bisphosphonates for prevention of CTIBL in breast cancer have informed both UK and European guidelines on management. A large randomized trial of denosumab, an antibody to RANK ligand, in prostate cancer has demonstrated prevention of bone loss and a reduction in fractures. The data supporting the use of bone-targeted agents in prevention of metastasis are less consistent, with variable findings from the randomized controlled trials in both breast and prostate cancer reported to date. However, the emerging evidence suggests that modification of the bone microenvironment does influence the clinical course of both early breast cancer and castrate-resistant prostate cancer, particularly in clinical settings in which bone metabolism is no longer primarily regulated by reproductive hormones. The role of bisphosphonates in CTIBL in breast cancer is now defined, but in other malignancies more evidence is needed prior to recommendation as standard treatment. In the role of preventing metastasis, results of ongoing studies are awaited to help clarify populations of patients who will derive benefit. Alternative therapies including the RANKL inhibitor denosumab may provide an alternative adjuvant treatment strategy. Combination therapy with adjuvant bone-targeted agents is yet to be investigated.