The patients were randomized in balanced fashion to double-blind treatment with exemestane plus placebo or exemestane plus entinostat. By study design, P values < 0.1 were considered statistically significant. Demographically, the patients were 62 years old on average. Eighty-five percent had experienced progression on an AI in the metastatic setting.
With a median follow-up of 18 months, entinostat was associated with longer median progression-free survival (4.28 vs 2.27 months; HR, 0.73; P = 0.06), with similar findings in subgroups stratified by locally advanced vs. metastatic disease, age, and site of metastasis, Dr. Yardley reported.
In 49 patients, blood samples collected before and during the first cycle of therapy were analyzed to determine the percent change of lysines in peripheral blood mononuclear cell proteins that were acetylated. Results showed that progression-free survival was greatest, at 8.54 months, among entinostat-treated patients who had hyperacetylation, defined as an abovemedian percent change in lysines that were acetylated during the first cycle of treatment.
These findings “suggest that entinostat-induced hyperacetylation appeared to track with improved outcomes in these patients and suggest quite provocatively within the very first cycle of treatment that this may be a potential marker to assess the benefit from this treatment,” said Dr. Yardley.
In an analysis that was exploratory because follow-up is still short, entinostat was also associated with better overall survival (26.9 vs 20.3 months; HR, 0.56; P = 0.027). Additional data with longer follow-up will be reported at the San Antonio Breast Cancer Symposium later this year.
The combination of entinostat and exemestane was well tolerated, with no unexpected safety signals. The most common grade 3/4 adverse events in the entinostat group were fatigue (13%), neutropenia (13%), nausea (5%), and vomiting (5%). The rate of discontinuation because of adverse events was 1% in the placebo group and 11% in the entinostat group.
Dr. Yardley reported no relevant conflicts of interest. Syndax Pharmaceuticals, developer of entinostat, was not among Dr. O’Shaughnessy’s disclosures.
Measure of bone metastases predicts breast cancer survival
The more metabolically active a woman’s bone metastases of breast cancer are on imaging, the greater her risk of death, researchers reported at the symposium.
In a retrospective cohort study of 269 women with newly diagnosed metastatic breast cancer, those whose bone metastases were “hotter” on a PET/CT—as assessed from maximum standardized uptake value (SUV-max)— had poorer overall survival. Compared with their counterparts with values in the bottom tertile of SUV-max values, women with values in the middle and top tertiles were roughly two to three times more likely to die after other prognostic factors were taken into account.
“To our understanding, this is the first large retrospective series to correlate SUV-max at metastatic breast cancer diagnosis with overall survival,” said lead author Dr. Komal Jhaveri of Memorial Sloan-Kettering Cancer Center, New York.
The risk of death also rose with increasing tertile of SUV-max in liver, lung, and lymph node metastases, but those associations were not signifycant. Their nonsignificance may have been due to the smaller numbers of patients having metastases in those sites, she said.
Session chair Dr. Robert R. Kuske, a radiation oncologist with Arizona Breast Cancer Specialists in Scottsdale, noted that SUV-max is a surrogate for how rapidly the tumor cells are proliferating and, hence, the tumor’s aggressiveness.
“So there should be a strong correlation between this SUV on the PET and the Ki-67 [histologic proliferation index],” he said. “This gives us another tool to evaluate how patients are going to do,” he commented. “Now [oncologists] can look at a metastasis on PET, measure the SUV, and get a handle on what the future of that patient is going to be—is it going to be a rapid slide to death, or is it going to be a very slow, indolent progression maybe over 10 or 15 years. And they can tailor the therapy based on the aggressiveness of the disease.” The PET/CT is usually done to determine whether the patient has metastases, so this additional prognostic information “is a little something extra you get from the test.”
Will these new findings be practice changing?
“I’ll start looking at SUV values in my patients with newly diagnosed metastasis,” said Dr. Kuske. “Yes, it will change my practice.”
In the study, Dr. Jhaveri and her coinvestigators reviewed records for women with metastatic breast cancer diagnosed between 2001 and 2008 who had a PET/CT scan performed within 60 days of the detection of metastases; had at least one avid metastasis in bone, liver, lung, or lymph node; and had not received chemotherapy in the month before the scan. Prior or current hormonal therapy was permitted.