By ecancer reporter Jo Armstrong

Presentation: Should bone targeted treatment be used in the adjuvant setting? - R Coleman

Bisphosphonates and denosumab are potent inhibitors of bone resorption that reduce the risk of skeletal complications and prevent treatment induced bone loss. Recent data suggest they may also modify the course of the disease and disrupt the metastatic process, reducing the risks of disease recurrence. This is thought to be via indirect inhibitory effects on the 'vicious cycle' of growth factor and cytokine expression between tumour and bone cells within the bone marrow microenvironment. Additionally, effects on the stem cell niche, direct effects on the cancer and immune modulation have all been suggested as relevant contributory factors.

In vitro studies have shown that bisphosphonates induce tumour cell apoptosis and inhibit tumour cell adhesion, invasion, proliferation and angiogenesis. In vivo animal studies show that bone targeted therapies can prevent establishment of bone metastases. Bisphosphonates also appear to enhance the anti-tumour activity of cytotoxic drugs in a sequence dependent manner.

In the early disease setting, improvements in disease free survival have been seen in several clinical trials of adjuvant bisphosphonates. The evidence is particularly strong in premenopausal women with endocrine responsive disease. Additionally, supportive clinical data have been reported from patients who received neoadjuvant chemotherapy +/- zoledronic acid in the ongoing AZURE trial. A smaller residual invasive tumour size and a higher rate of pathological complete response was observed in those patients receiving zoledronic acid in addition to chemotherapy.

A neoadjuvant biomarker study has been performed to evaluate the effects of chemotherapy followed by zoledronic acid on proliferation, angiogenesis markers and apoptosis and studies to evaluate the potential for denosumab to prevent metastasis are in progress.

The potential anti-tumour and disease-modifying roles of adjuvant bone targeted therapies hold great promise. Bone targeted agents may have anticancer activity but results from recently completed large adjuvant trials must be awaited before their routine use in the adjuvant setting can be recommended.