Bone metastases are more common in advanced breast cancer, and patients’ bone health will be severely compromised by the tumor. Clinically, bisphosphonates are effective in preventing and treating bone-related events in breast cancer, such as increased bone pain, pathological fractures, spinal cord compression, and hypercalcemia. The main drugs commonly used are zoledronic acid and pamidronate.
In addition to bisphosphonates, there is a drug called denosumab (Denosumab) that treats bone metastases from breast cancer, is easily injected subcutaneously, and does not require routine monitoring of kidney function during treatment.
In November 2010, denosumab was approved by the US Food and Drug Administration (FDA) for the prevention of bone-related events in patients with bone metastases from solid tumors, and breast cancer is also in the indication. Patients with breast cancer on aromatase inhibitors are at increased risk of fracture and may be considered for denosumab to increase bone mass.
The role of denosumab is also recognized by guidelines: the 2018 National Comprehensive Cancer Network (NCCN) guidelines for the management of breast cancer, as well as the Chinese Society of Clinical Oncology (CSCO) guidelines for the management of breast cancer, mention the option of denosumab for patients with bone metastases from breast cancer.
Denosumab is not currently available in China, but relevant clinical studies are ongoing. What does it do? How does it work? This article will take you through this drug.
How does denosumab work?
How does denosumab work?
The human skeleton is constantly removing old bone tissue and replacing it with new bone, a process called bone remodeling. Bone remodeling is driven by two major factors: osteoclasts (which destroy bone) and osteoblasts (which build new bone). Denosumab can prevent osteoporosis and protect bone health by preventing osteoclasts from maturing and interfering with the “bone breaking” process.
Bone metastases from breast cancer, denosumab delays adverse bone events
Zoledronic acid is widely used for bone metastases from breast cancer. Denosumab has shown better therapeutic efficacy compared with zoledronic acid. For patients with breast cancer bone metastases, the time to first bone-related event was significantly later under denosumab treatment than zoledronic acid, and denosumab reduced the risk of first bone-related adverse events by 18%.
The NCCN guidelines state that patients should take vitamin D and calcium supplements while on denosumab, and in addition, given the risk of osteonecrosis of the jaw with denosumab therapy, an oral examination and appropriate precautions prior to dosing are recommended.
Endocrine therapy increases fracture risk, denosumab to address it
Patients with breast cancer are at risk for decreased bone mineral density and adverse bone events during treatment with endocrine drugs such as aromatase inhibitors, which in severe cases can even offset the survival benefit of endocrine therapy.
Denosumab has a specialty in dealing with this “problem.” The ABCSG-18 study demonstrated that denosumab is safe and effective in preventing the risk of fractures caused by aromatase inhibitors. The study enrolled 3420 hormone receptor-positive breast cancer patients on long-term endocrine therapy with non-steroidal aromatase inhibitors. The results showed that patients with concomitant denosumab had a significant delay in time to first fracture and a 50% reduction in the risk of first fracture in patients with concomitant denosumab.
The ABCSG-18 study also found that denosumab increased bone mineral density in breast cancer patients, most notably in the lumbar spine, with a 10.02% increase in bone mineral density, followed by the hip (7.92%) and femoral neck (6.51%).
Safety-wise, there was no increase in adverse effects with denosumab and no osteonecrosis of the jaw. This study is still ongoing and will provide more evidence of efficacy and safety in the future.
Another study focusing on bone strength in breast cancer patients showed a significant increase in lumbar spine bone density (7.6% improvement) after 2 years of denosumab application in patients. Regardless of the type of endocrine therapy, patients benefited from denosumab, with improvements in bone density in multiple body parts.
Denosumab is still being explored
The use of denosumab in patients with early-stage breast cancer is still being explored. For example, can denosumab prevent bone density loss in early-stage breast cancer patients treated with aromatase inhibitors after surgery, and can denosumab prevent bone metastases after surgery in high-risk early-stage breast cancer patients?
Summary
Denosumab is not yet available in China, but domestic and international guidelines state that denosumab can be considered for the prevention and treatment of bone-related events in breast cancer bone metastases. This recommendation is worthy of consideration.
For postmenopausal female patients on aromatase inhibitors, denosumab may reduce the risk of fracture and improve bone mineral density in several parts of the body, with implications for breast cancer endocrine therapy.