US-based study led by University College Cork researcher
An Irish-led study has found promising results for a new drug combination in the treatment of advanced HER2-negative breast cancer.
A histone deacetylase (HDAC) inhibitor is a drug that causes a chemical change to stop tumour cells from dividing. When combined with two types of immunotherapy known as checkpoint inhibitors, the treatment led to one-in-four women having their tumour destroyed or significantly reduced.
The study was led by Prof Roisin Connolly of University College Cork’s cancer research facility, while based in the US at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center.
The multi-centre study included 24 women with HER2-negative metastatic breast cancer. Twelve had hormone receptor-positive disease, and 12 had triple negative disease. All received entinostat plus two types of immunotherapy: the PD-1/PD-L1 inhibitor nivolumab and the CTLA-4 inhibitor ipilimumab.
The study team, who aimed to improve response to immune checkpoint inhibitors by sensitising the tumour microenvironment, found that the combination therapy resulted in a 25 per cent overall response rate in women with advanced HER2-negative breast cancer. Half of the participants also went six months without their disease worsening.
Among trial participants with triple-negative breast cancer, an overall response rate of 40 per cent was found. If confirmed in larger trials, these tumour responses are significant, as advanced breast cancer – in particular the triple-negative subtype which represents up to15 per cent of all breast cancers – remains an area of unmet clinical need, due to a lack of effective therapies.
“This clinical trial highlights the importance of interdisciplinary collaboration to bring an exciting hypothesis from the laboratory to the clinic, and sets the scene for future trials investigating novel treatment approaches for this patient population,” said Prof Connolly.
Co-author Dr Elizabeth Jaffee added: “To our knowledge, this is the first published study that investigates treatment with an HDAC inhibitor in combination with dual immune checkpoint inhibitor therapy in patients with advanced breast cancer.
“Heavily pretreated advanced breast cancer remains an area of unmet need and a combination strategy that results in the ORR and PFS described is of interest.”
The study’s resulting research paper ‘Entinostat, nivolumab and ipilimumab for women with advanced HER2-negative breast cancer: a phase Ib trial’, was published this week in the journal Nature Cancer.