Novel Drug Combination Shows Promising Results for Patients With HER2-Negative Breast Cancer

A novel three-drug combination has shown notable responses in patients with advanced HER2-negative breast cancer.

The treatment involves a “histone deacetylase (HDAC) inhibitor – a drug that causes a chemical change to stop tumor cells from dividing – with two types of immunotherapy known as checkpoint inhibitors, which unharness the power of the immune response against cancer.”

The study found that the combination therapy “resulted in a 25% overall response rate (ORR) in women with advanced HER2 (human epidermal growth factor receptor 2)-negative breast cancer. This means that for 25% of women who received the therapy, their cancer was destroyed or significantly reduced.” Meanwhile, patients with triple-negative breast cancer, who historically have fewer treatment options, had an ORR of 40%.

The treatment’s response to checkpoint inhibition in metastatic breast cancer is very promising and “warrants further clinical evaluation in a phase II study,” according to lead author Evanthia Roussos Torres, M.D., Ph.D. The study “met its primary endpoint of safety by demonstrating that there were expected and tolerable toxicities among patients, with none requiring discontinuation of therapy.” Half of the participants’ disease “did not worsen for at least six months.”

Co-author Elizabeth Jaffee, M.D., stated that 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.”

Immune checkpoint inhibitors have become “cornerstones of treatment” in patients with solid tumors “by releasing the inhibition function of various types of immune cells and allowing patients’ immune systems to attack cancer cells. This strategy has so far been ineffective for most breast cancers.” On the other hand, “epigenetic drugs that silence the genes involved in cancer development have been studied with single immune checkpoint inhibitors for breast cancer to change the immune response to the tumor microenvironment.”

Roussos Torres, the study’s lead author, emphasized that it is unclear if the good responses seen in the study came from “changing the tumor microenvironment.” She also highlights the “need for a deeper investigation of the breast cancer tumor microenvironment with a focus on changes in myeloid (immune) cell populations to determine their role in sensitization of the tumor microenvironment to treatment with immune checkpoint inhibitors.”

Of the 300,000 people in the United States that receive a breast cancer diagnosis each year, about “70% are hormone receptor-positive and HER2-negative.” Only 10% to 15% are “triple negative, meaning tumor cells have no hormone receptors and low HER2 levels, making them more difficult to treat than other types of breast cancer.”

Johns Hopkins Medicine’s website has the news.