Promising Results for Enzalutamide in Triple-Negative Breast Cancer

The prostate cancer drug enzalutamide has shown activity in a subset of women with advanced triple-negative breast cancer whose tumors express the androgen receptor (AR). The results of the phase II single-arm trial (abstract 1003) were presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting held May 29 to June 2 in Chicago.

“Enzalutamide is an oral therapy and extremely well tolerated. We are seeing impressive improvements in progression-free survival [PFS] and in the clinical benefit rate,” said study presenter Tiffany Traina, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York, who specializes in breast cancer.

The trial enrolled 118 women with AR-positive triple-negative breast cancer. More than 50% of the patients received enzalutamide as either a first- or second-line therapy for their metastatic disease. Patients were treated with 160 mg of enzalutamide daily until disease progression.

The trial met its primary endpoint of clinical benefit at 16 weeks of therapy. Of the 75 patients who could be evaluated, 35% achieved a clinical benefit. There were two complete responses and seven partial responses. The clinical benefit rate at ≥ 24 weeks was 29%. The median PFS was 14.7 weeks.

Data on a subset of patients from the trial were originally presented at the 2014 San Antonio Breast Cancer Symposium, but the current results are the first of the entire clinical trial population to be presented.

The AR is present in many cases of invasive breast cancer. Unlike the estrogen receptor, which is not expressed in women with triple-negative disease, about 20% to 40% of triple-negative breast tumors express the AR.

Triple-negative breast cancer is generally treated with cytotoxic chemotherapies because there have not been any molecular targets identified to treat this heterogeneous group of tumors. “There is a clearly replicated subset of tumors within triple-negative breast cancer that are driven by the androgen receptor and it behaves like a hormonally driven subtype of cancer,” said Traina.

The 47% of patients on trial whose tumors stained positive for AR expression and who had an AR-related gene signature had better outcomes, including an improved overall survival, compared with those whose tumors were AR-positive but did not have the gene signature. Patients who were positive for this gene signature had a median PFS of 16 weeks compared with 8 weeks in patients whose tumors lacked the gene signature.

“AR by immunohistochemistry is not perfect in predicting who is going to respond. This is not the whole story. We found that even those with really low AR expression level have had great responses [on trial],” said Traina. “Combining AR expression with the gene signature has allowed us to enrich for the population that appears to truly benefit from enzalutamide,” she added.

The most common drug-related adverse events were fatigue (34%), nausea (25%), decreased appetite (13%), diarrhea (10%), and hot flush (10%). The only high-grade adverse event that occurred in at least 5% of patients was fatigue (5%).

“This is the most exciting data we have had in triple-negative breast cancer and certainly supports moving this therapy forward in development,” said Traina.