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Combination of androgen receptor blocker and aromatase inhibitor benefits some women with hormone receptor-positive breast cancer, phase 2 trial finds

  • The first randomized clinical trial of the drug enzalutamide in women with hormone receptor-positive (HR+) breast cancer has shown that a combination of enzalutamide and exemestane can keep the disease in check longer than exemestane alone in certain patients, Dana-Farber Cancer Institute researchers reported at the San Antonio Breast Cancer Symposium.

    Enzalutamide inhibits the ability of the androgen receptor (AR) — a protein spurred to action by androgen hormones — to signal cancer cell growth. It is used to treat men with metastatic prostate cancer whose disease doesn’t respond to androgen-blocking drugs. Its potential as a breast cancer treatment stems from a surprising research finding: more than 75 percent of breast cancers laden with receptors for the female hormones estrogen and progesterone also carry the AR. Breast cancers that grow in response to AR signaling are often resistant to therapies that block estrogen or progesterone.

    Drugs such as enzalutamide, which hinder androgens from activating the AR, are thought to hold promise for halting or slowing the growth of such cancers. In an earlier study, enzalutamide was found to be active in patients with advanced triple-negative breast cancer that tested positive for AR.

    The current study, a phase 2 clinical trial, compared enzalutamide and exemestane, an aromatase inhibitor, to exemestane alone in patients with advanced or metastatic HR+ breast cancer. The patients were divided into two groups based on whether they had or had not previously been treated with endocrine therapy (which blocks estrogen or progesterone). A genetic biomarker enabled researchers to determine which patients’ tumors had active AR signaling. Such tumors were thought to be more likely to respond to combined enzalutamide and exemestane.

    A total of 247 patients participated in the study. A significant improvement in progression-free survival (the length of time before the disease began to worsen) was seen in patients who had not received prior endocrine therapy and whose tumors carried the biomarker for AR signaling. Within that group, patients who received the combination therapy had a median progression-free survival of 16.5 months, compared to 4.5 months for those who received exemestane alone. The combination did not appear to improve progression free survival in patients whose tumors did not carry the biomarker or those who had previously received endocrine therapy. The combined therapy was well tolerated by study participants.

    "This is the first study to show that an androgen receptor inhibitor may be able to improve outcomes in patients with hormone receptor positive breast cancer that has active androgen receptor signaling. Because this was a relatively small study, we first need to confirm these results in additional trials. However, if these results are confirmed, it could lead to an important new therapy for this very common type of breast cancer," says the study’s lead author, Ian Krop, MD, PhD, of Dana-Farber.

Posted on December 08, 2017

  • Ian E Krop
  • Research
  • Breast Cancer
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  • Ian Krop, MD, PhD

    Ian Krop, MD, PhD