Denosumab is safe and effective for giant cell bone cancer

International Lancet Oncology trial findings indicate denosumab (Xgeva®) is safe and effective in giant cell bone cancer.

Medical science gains new momentum every day and works intensively to demonstrate that no disease affecting humanity is untreatable. Cancer remains one of the diseases against which medical science has fought hard in recent years and achieved very positive results. As the search continues for solutions to cancer, some types of which pose a particular risk to life when not detected early or treated, denosumab, thought to be effective against giant cell bone cancer, has produced positive treatment responses in research.

According to initial research results published in Lancet Oncology, denosumab (Xgeva®) has proven safe and effective against giant cell bone cancer, a highly aggressive cancer. Indeed, in surgically treated patients, %96 were found to have no disease progression after an average observation period of 13 months.

Bone mass is important because it maintains skeletal integrity and the ability to move, provides support for muscles, and acts as a store for mineral ions. Bone tissue is renewed throughout life as bone-destroying cells (osteoclasts) break it down and bone-forming cells (osteoblasts) replace it with new tissue. This remodeling is maintained through bone formation and breakdown and various connections between cells. The nature of the signals and protein mediators sent between cells is therefore important.

Research in previous years has shown that a protein known as RANK ligand plays an important role in bone breakdown. Giant cell bone cancer is directly associated with RANK ligand, which causes bone breakdown. This cancer generally affects young adults aged between 20 and 40. In the past, after surgery, which was the only treatment option offered to patients with giant cell bone cancer, the disease either recurred or patients had to endure devastating consequences such as amputation (removal of a limb). Indeed, %25-30 of these patients subsequently underwent joint replacement surgery (a prosthesis to replace the lost limb).

What is denosumab used for?

This targeted monoclonal antibody blocks RANK ligand, preventing bone destruction and eliminating potential giant cells. It prevents bone complications in patients whose cancer has spread there.

The study enrolled 282 histologically confirmed patients in three groups;

• Group I.: Surgically salvageable giant cell bone cancer
• Group II.: Surgically salvageable disease with severe surgical consequences such as loss of jointed organs
• Group III.: Patients from a previous denosumab study

The first two groups received monthly treatment with initial periods at days 8 and 15, subcutaneous 120 mg denosumab. The third continued previous dosing. Primary endpoint was safety; secondary endpoints were the proportion avoiding surgery at six months and time to progression.

After average follow-up of 13 months, in the first group, %96 of patients (that is, out of 169 patients, 163 patients) had no disease progression. In the second group, %74 of patients (that is, out of 100 patients, 74 patients) did not need any surgery, and among patients in that group who underwent surgery, %62 (that is, out of 26 patients, 16 patients) suffered less damage than planned. Overall, %72 of all patients had an objective response to denosumab.

Only %1 of patients in the study developed jaw bone collapse (osteonecrosis) resulting from blocked blood flow to the bones, while %5 developed reduced blood calcium levels (hypocalcemia). The most common side effects were low phosphate levels, back pain, pain in the hands and feet, skeletal muscle pain, and anemia. More serious side effects were identified in %9 of patients, but no treatment-related risk of death was found.

Conclusion

Looking at the initial results, I am hopeful that denosumab will become a new treatment option in the future, considering its positive response against giant cell bone cancer and its effectiveness in reducing the destructive consequences of surgery. Such an expansion of treatment options, particularly in cancers that are difficult to manage, means another obstacle has been removed and another solution found. I hope you will always remember this..