INCORPORATING A CDK 4/6 INHIBITOR into standard care delays disease progression for people with metastatic hormone receptor (HR)-positive, HER2-positive breast cancer, according to study results presented at the San Antonio Breast Cancer Symposium (SABCS) Dec. 12.

About 10% of people with breast cancer have HR-positive, HER2-positive disease, according to the National Cancer Institute. When the cancer has spread to other parts of the body, standard care calls for a treatment combination that affects both the estrogen and HER2 pathways. However, patients often develop resistance to anti-HER2 therapies, forcing them to switch to other treatments that can have more difficult side effects, such as chemotherapy.

Evidence from preclinical studies has suggested CDK 4/6 inhibitors could prevent treatment resistance, allowing patients to remain on the treatment combination longer. Researchers tested one specific CDK 4/6 inhibitor, Ibrance (palbociclib), and analyzed how it impacted progression-free survival in this population.

In a phase III clinical trial, researchers followed 518 people with metastatic HR-positive, HER2-positive breast cancer who had received an initial bout of six to eight rounds of chemotherapy and anti-HER2 therapy. Participants were randomized to receive either anti-HER2 therapy and endocrine therapy alone or Ibrance with anti-HER2 therapy and endocrine therapy. For anti-HER2 therapy, participants took Herceptin (trastuzumab) with or without Perjeta (pertuzumab), and for endocrine therapy, they could receive either an aromatase inhibitor or fulvestrant.

After a median follow-up of 53 months, people who received Ibrance had no disease progression for 44.3 months, compared with 29.1 months for those who had standard care—a 15.2-month difference. The Ibrance group also had better five-year overall survival (74.3% vs. 69.8%) and overall response (29.2% vs. 22.2%) rates than people who received standard treatment. Diarrhea, fatigue, mouth inflammation and low white blood cell levels occurred more often in participants who took Ibrance.

“This may represent a new standard of care for patients diagnosed with [HR+], HER2+ breast cancer,” Otto Metzger, a study author and a medical oncologist at Dana-Farber Cancer Institute in Boston, said during a conference press briefing. Metzger said he thinks this treatment should be widely available for people with metastatic HR-positive, HER2-positive disease, so he and his colleagues plan to file for approval for this indication from the Food and Drug Administration. Ibrance is currently approved for use in people with advanced HR-positive, HER2-negative breast cancer.

While the trial’s findings suggest this CDK 4/6 inhibitor can benefit this population, Metzger cautioned against assuming the same may be true for other drugs in this class. He noted most CDK 4/6 inhibitors have not been tested for this indication in a phase III clinical trial.

Virginia Kaklamani, leader of the breast cancer program at the UT Health San Antonio MD Anderson Cancer Center and SABCS co-director, said people with this type of breast cancer now typically live a long time after their diagnosis, so she views treatment as “a marathon and not a sprint.” With that in mind, any therapy that helps prevent drug resistance can benefit patients. “Treatments such as this that, in a sense, delay the use of chemotherapy … are extremely welcome to the community and to the physicians and to the patients,” said Kaklamani, who was not involved in the study.

Drugs that postpone the need for chemotherapy can help people avoid chemo’s common side effects, including appetite changes, fatigue, hair loss, infection, nausea and vomiting, and numbness or tingling in the arms or legs. “These regimens are important because they help maintain the quality of life of our patients for a longer period of time,” Kaklamani said.

Thomas Celona is an editor at Cancer Today.