Existing cancer drugs to be trialled as new treatment for breast cancer

Two drugs that are already being used separately in the treatment of some prostate, renal and skin cancers, will now be tested in combination for the first time for breast cancer
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A new clinical trial led by the University of Sheffield could bring hope to thousands of UK women living with incurable secondary breast cancer, also known as metastatic or stage-IV breast cancer.

Two drugs that are already being used separately in the treatment of some prostate, renal and skin cancers will now be tested in combination for the first time for breast cancer, to see if they improve outcomes for women with breast cancer that has spread to other parts of the body.

Led by Professor Janet Brown at the University of Sheffield, and run by the Leeds Clinical Trials Research Unit, the study team will give radium-223 and avelumab to 42 women with breast cancer that has spread to other parts of their body, including the bones.

Secondary or metastatic, breast cancer occurs when breast cancer cells spread from primary cancer in the breast, through the lymphatic or blood system to other parts of the body, or secondary sites.

While 99 per cent of women diagnosed with breast cancer at stage-I will survive for five years or more following diagnosis, this figure drops to just 27 per cent for women who are diagnosed with secondary breast cancer. It is not currently known how many people have secondary breast cancer. However, estimates suggest 35,000 people in the UK are living with the incurable disease.

Professor Brown and her team will investigate if the combination of radium-223 and avelumab produces an improved immune response to secondary breast cancer in the bone and other sites in the body, causing tumours to shrink.

Avelumab is currently used to treat some forms of secondary renal and secondary skin cancers, whilst radium-223 is used to successfully treat prostate cancer when it spreads to the bones.

The study is being funded by the Breast Cancer Now Catalyst Programme, which aims to accelerate progress in world-class breast cancer research through innovation and collaboration. As part of the Programme, Pfizer has provided Breast Cancer Now with funding through an independent medical research grant and given the charity’s researchers access to several Pfizer medicines.

Professor Janet Brown, Chair, Medical Oncology and Professor, Translational Medical Oncology, University of Sheffield, said, “Although radium-223 and avelumab are approved for the treatment of other cancers, they have not been previously used in combination for breast cancer patients.

“We hope that this trial will see this combination treatment improve the immune response to secondary breast cancer in the bones and other sites in the body, as earlier research has suggested it could.

“This trial is an exciting chance to see if we can make immunotherapy work better, causing tumours in the bone and other secondary sites to shrink, which would significantly improve outcomes for people with secondary breast cancer.”

The immune system plays an important role in destroying cancer cells, but cancer cells can evade the immune system to survive. Immunotherapies, like avelumab, are medicines that help the immune system to recognise and attack cancer. Avelumab is an immunotherapy drug called a PD-L 1 inhibitor, which blocks the PD-L 1 protein, a protein which is found on some cancer cells. The PD-L 1 protein decreases the immune system’s ability to kill cancer cells, so by blocking the PD-L 1 protein, the immune system can be stimulated to recognise and destroy cancer cells.

Radiotherapy can improve the immune system’s response to immunotherapy, but it is difficult to target radiotherapy only to tumours in the bones. Radium-223 is different to conventional radiotherapy as the radioactive drug is absorbed by bone cells, so that it delivers the treatment closer to where it is needed, inside the body near to the tumour.

Dr Simon Vincent, Director, Research, Support and Influencing, Breast Cancer Now, said, “When breast cancer spreads to another parts of the body such as the bones, brain, lungs or liver, it becomes incurable. We desperately need to find new and effective treatments for thousands of women living with this devastating disease.

“Professor Brown’s research is particularly promising, as both radium-223 and avelumab are already being used to treat people with other types of cancer. We, therefore, hope that if the trial is successful, this drug combination could be tested in larger trials and could improve the chances of survival for people with secondary breast cancer in the future.

“This trial is one of the many exciting research projects being funded by The Breast Cancer Now Catalyst Programme. Charity-funded medical research has been served a huge blow by both Brexit and the COVID-19 pandemic, but through this programme, we are continuing to accelerate progress in world-class breast cancer research.”

avelumabbreast cancer treatmentCancer Drugsclinical trialUniversity of Sheffield
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