Adding Everolimus Doubles PFS in AI-Resistant Metastatic Breast Cancer

Photo © SABCS / Todd Buchanan 2016. Noah S. Kornblum, MD, discussing the results.

The addition of everolimus to fulvestrant was associated with more than a doubling of progression-free survival (PFS) in women with metastatic hormone receptor–positive, HER2-negative breast cancer who were resistant to aromatase inhibitor (AI) therapy, according to a study presented today at the San Antonio Breast Cancer Symposium (SABCS), held December 6–10 in San Antonio, Texas.

Though AI therapy is highly effective, “resistance to AI therapy ultimately develops in most patients,” said Noah S. Kornblum, MD, of Albert Einstein College of Medicine in New York, who presented the study and spoke during a press conference. “One strategy for addressing AI resistance is targeting the PI3K-AKT-mTOR pathway,” such as with the mTOR inhibitor everolimus.

The PrECOG 0102 trial included 130 postmenopausal women (of 131 randomized) with hormone receptor–positive, HER2-negative metastatic breast cancer; all included had AI-resistant disease, normal organ function, and an ECOG performance status of 0–1. Notably, two doses of fulvestrant were allowed within 28 days prior to randomization. All patients received fulvestrant and were randomized to receive either everolimus or placebo. An analysis was conducted after 98 patients had disease progression.

At that point, the median PFS was 10.4 months among those receiving everolimus, and 5.1 months among placebo patients, meaning the primary endpoint of the trial was met.

Toxicity was increased with everolimus, however. Among those patients, 53% experienced a grade 3 adverse event, compared with only 23% of those receiving placebo. The most common grade 3/4 adverse events included hyperglycemia, stomatitis, hypertriglyceridemia, and others. Corticosteroid mouthwash prophylaxis was not used, which can reduce the burden of stomatitis.

Virginia G. Kaklamani, MD, of the UT Health Science Center in San Antonio and co-director of SABCS, stressed during the press conference that stomatitis in particular is a clinically meaningful issue when women receive everolimus for extended periods of time. “The more we use these drugs that are very tricky, the better we become at dealing with the side effects,” she said.

Importantly, this trial was conceived and initiated before the US Food and Drug Administration approval of palbociclib, a CDK4/6 inhibitor, for treatment of hormone receptor–positive metastatic breast cancer. Further studies on other combinations are still needed in this new treatment landscape. “These pathways are complex,” Kornblum said. “My personal opinion is that this is likely to become a good treatment option for women.”