The combination of everolimus and exemestane was deemed generally tolerable with a manageable safety profile in women with advanced HR-positive/HER2-negative breast cancer.
The combination of everolimus and exemestane was deemed generally tolerable with a manageable safety profile similar to previous trials in women with hormone receptor–positive, HER2-negative advanced breast cancer who progressed during or after non-steroidal aromatase inhibitor therapy. This is the largest safety dataset on this therapy combination.
“The pivotal BOLERO-2 trial showed that dual-blockade with everolimus, an mTOR inhibitor, plus exemestane more than doubled median progression-free survival vs exemestane alone,” wrote study authors led by Guy Jerusalem, MD, PhD, of Liege University in Belgium.
The new BALLET study was a phase IIIb, expanded-access multicenter, one-arm, open-label trial, that included 2,131 patients and was intended to assess the safety of the everolimus plus exemestane regimen. The authors noted that this patient cohort was more heavily pretreated than that of the BOLERO-2 study. The results were published online ahead of print in Annals of Clinical Oncology.
After censoring patients who discontinued treatment for various reasons, the median treatment duration was 5.1 months with everolimus and 5.3 months for exemestane. In total, 94.7% of patients experienced at least one adverse event (AE); 42.7% of patients had at least one grade 3/4 adverse event. Of all the AEs, 81.8% were related to everolimus, and 15.1% were related to exemestane.
The most common non-hematologic AE was stomatitis, occurring in 52.8% of patients (50.8% were everolimus-related); this was followed by asthenia (22.8%, 14.6% everolimus-related). Anemia was the most frequently reported hematologic AE, in 14.4% of patients, followed by thrombocytopenia (5.9%, 4.6% everolimus-related).
The researchers compared the general study population to a subset of elderly patients, and found that 95.2% of the elderly patients experienced at least one AE. The most common AE in elderly patients compared to younger patients included stomatitis, asthenia, and reduced appetite.
A total of 29.6% of patients required an everolimus dose reduction; only 1.2% required an exemestane dose reduction. Similarly, dose interruptions for everolimus were required in 55.9% of patients, but only 19.3% for exemestane. Most of the patients who needed an everolimus interruption were able to restart the drug at the full dose. A permanent treatment discontinuation was required in 17.1% of patients due to AEs; most of those occurred within 3 months of treatment initiation.
The elderly subset were more likely to need a dose reduction or interruption. Of the elderly cohort, 37.7% required a reduction, and 60.5% required a dose interruption, compared with 26.7% and 54.2% in the younger patients.
“Given the early incidence of AE and dose interruption/modification observed in BALLET, close follow-up in the first months of therapy is indicated,” the authors wrote. “We recommend a first visit 2 weeks after starting everolimus,” they added, “in order to further reduce everolimus-related discontinuation rate.”
The results of this study are encouraging for this regimen in that no new safety signals were found in this largest-ever cohort of these patients. “Diligent monitoring, proactive communication, early detection and implementation of appropriate AE-management strategies can ensure better treatment optimization,” the authors concluded.