Testing a combination of CDK4/6 inhibitor and immunotherapy to treat triple negative breast cancer

To achieve our aim that by 2050 everyone who develops breast cancer will live and be supported to live well, we need to speed up the translation of research in the lab into new and effective treatments for patients. We’re bringing together leading researchers and top pharmaceutical companies to pool ideas and resources and ultimately stop people dying from breast cancer.

The Breast Cancer Now Catalyst Programme

As part of the Breast Cancer Now Catalyst Programme, we have collaborated with leading pharmaceutical company Pfizer to give researchers unprecedented access to a number of Pfizer’s licensed and investigative drugs as well as vital funding for researchers to test these drugs. This allows us to combine the expertise of our researchers with Pfizer’s compounds and deliver new treatments to patients more quickly.

Triple negative breast cancer accounts for approximately 15% of breast cancers. It can be more aggressive than other types of the disease and there are currently limited treatment options available. We need to develop new and effective ways to treat triple negative breast cancer and to breast cancer coming back and spreading throughout the body.

Drug: Palbociclib

• Blocks the activity of proteins called CDK4 and CDK6, which prevents cells from multiplying
• Currently in Phase III trials in combination with other drugs for high risk early breast cancer
• Already used to treat oestrogen receptor positive (ER+) HER2 negative breast cancer that has spread, in combination with hormone (endocrine) therapy

Drug: Avelumab

• Blocks the PD-L1 protein, which is found on some cancer cells and decreases the immune system’s ability to kill cancer cells
• It is currently used to treat some forms of bladder and secondary skin cancer

Studying the activity of different genes in triple negative breast cancer cells helped researchers to divide triple negative breast cancers into sub-types. One sub-type of triple negative breast cancer has high levels of a protein called androgen receptor. Several drugs targeting androgen receptor have been tested in small trials without much success. Professor Nicholas Turner is looking for better ways to treat this specific sub-type of triple negative breast cancer and hopes a combination of immunotherapy and a drug called palbociclib could be the answer.

Nicholas and his team have already showed that palbociclib can be effective against triple negative breast cancer with high levels of androgen receptor. We also know that some triple negative breast cancers are sensitive to immunotherapy. He believes that palbociclib could make cancer cells more recognisable to the immune system, and in turn more susceptible to immunotherapy.

The researchers are now investigating if a combination of palbociclib and an immunotherapy drug avelumab is safe and effective against secondary triple negative breast cancer with high levels of androgen receptor. This sub-type of triple negative breast cancer is currently treated with chemotherapy.

If this research reveals that the combination of palbociclib and avelumab is safe and effective against a sub-type of triple negative breast cancer with high levels of androgen receptor, it could replace chemotherapy and provide a much-needed personalised treatment option. We hope that this approach could offer an effective treatment and give more people with triple negative breast cancer a better chance of survival.