The Bone Cancer Research Trust joined scientists, patient advocates, oncology experts, pharmaceutical companies, and regulators at the eighth Paediatric Strategy Forum to discuss the potential of a new treatment for osteosarcoma and Ewing sarcoma in children.

At the meeting, which is held to further drug developments for the treatment of children, 108 participants came together to discuss the use of multi-targeted kinase inhibitors (mTKIs) in children with bone cancer.

Previous research has established mTKIs as both effective single-drug treatment, or when used alongside chemotherapy, in adults. Now, future studies will focus on how mTKIs can be used in the treatment of osteosarcoma and Ewing sarcoma in children.

Randomised trials are set to explore the use of mTKIs in both first-line treatment and relapse cases, helping to develop the drug for paediatric medicine. Earlier findings have indicated that the toxicity of the drug is manageable in adult patients, and it is hoped that this will be consistent in children.

Zoe Davison, Head of Research, Information & Support at the Bone Cancer Research Trust, said:

We are delighted to have attended the eighth Paediatric Strategy Forum and be given the chance to participate in discussions that review the available data to determine future priorities and directions for bone cancer patients. The decisions made today on the critical next steps will provide fresh hope for children with osteosarcoma and Ewing sarcoma and their families. We know that, currently, patients face some of the most aggressive treatment options that have not changed in over thirty years, and our hope is that survival rates and quality of life will be improved by the findings from the next stage of crucial research.

What are we expecting from this research?

Bone tumours with specific kinase mutations respond well to targeted therapies, known as Tyrosine kinase inhibitors or TKIs, which inactivate the erroneous or overactive proteins that are produced in the cell as a result of particular mutations within cancer. However, recurrent specific kinase mutations have not been identified in osteosarcoma or Ewing sarcoma.

Because of this, mTKIs that are capable of inactivating several tyrosine kinase proteins at the same time could be the favourable treatment option for osteosarcoma or Ewing sarcoma. This is because TKIs are selective for a single receptor. Additionally, resistance to a single TKI can develop quickly. This is less likely to occur with mTKIs as they attack multiple targets simultaneously.

Plans to identify relevant biomarkers of response in mTKIs, alongside increasing understanding of osteosarcoma and Ewing sarcoma tumour biology, is expected to propel this treatment option forward for young patients. mTKIs with the greatest activity levels and tolerable toxicity levels that could be used in combination with chemotherapy are expected to be taken forward in the next stage of research.

Results from frontline studies such as INTER EWING-1, which is being led by Bone Cancer Research Trustee and world-renowned paediatric oncologist Professor Bernadette Brennan, will be crucial to the understanding of mTKIs in osteosarcoma or Ewing sarcoma.

What are multi-targeted kinase inhibitors (mTKIs)?

mTKIs are drugs designed to inactivate several tyrosine kinase proteins, which are either anchored on the surface or free inside the cancer cells. Because tyrosine kinase proteins interact with each other, using drugs that can inactivate several of them at once (mTKIs) are seen as the more efficient treatment approach. In addition, cancer cells can become resistant to treatment, or even bypass the inactivation of just one kinase protein. It is less likely that this will happen if several tyrosine kinase proteins are targeted at the same time.

Osteosarcoma and Ewing sarcoma are often treated with a combination of chemotherapy and additional therapies alongside surgery. In most cases, chemotherapy is given alongside additional drugs, such as Mifamurtide, to treat osteosarcoma.

Osteosarcoma is not very sensitive to radiotherapy, so it is only used when surgery to remove the tumour is not possible, or to control pain. Ewing sarcoma patients are usually treated with a combination of chemotherapy drugs prior to surgery. They will then receive radiotherapy if some of the tumour is still present in the body, or if more than 10% of the tumour is still alive when examined in the laboratory. Chemotherapy often continues post-surgery and can also be accompanied by proton beam therapy.

A review of the meeting has been published in the European Journal of Cancer and is freely available here.