At the American Society of Clinical Oncology (ASCO) Breast Cancer Symposium last week, Hope Rugo, MD, director of breast oncology and clinical trials education and professor of medicine at the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco, presented the updated 18-month results of the BOLERO-2 trial.
Earlier results from the trial showed that everolimus combined with exemestane, an aromatase inhibitor, resulted in improved progression-free survival in women with previously treated, advanced estrogen-receptor–positive breast cancer.
The BOLERO-2 trial compared everolimus, given at a dose of 10 mg per day in combination with the steroidal aromatase inhibitor exemestane at 25 mg per day to placebo plus exemestane. Patients were randomized two to one to either the experimental or the control arm, respectively.
The updated 18-month progression-free survival was 7.8 months for the everolimus arm compared to 3.2 months for the control arm of exemestane alone (hazard ratio = 0.45, P < .0001). These progression-free survival benefits were consistent for all subgroups analyzed, including age and geography. Patients with visceral metastases were a substantial portion of the overall trial and had a progression-free survival benefit comparable to the overall population.
Clinical benefit rates were double in the experimental group compared to the control group in the BOLERO-2 trial. “Response rate has been an allusive endpoint in second-line hormone therapy patients,” Dr. Rugo said during her presentation. Response rates were 1.7% in the exemestane-alone group compared to 12.6% in the everolimus group (P < .0001).
“This longer follow-up confirmed that the addition of everolimus to exemestane following progression on nonsteroidal aromatase inhibitors significantly improves progression-free survival, overall response rate, and response duration,” said Dr. Rugo.
Overall survival data continue to be promising and even more mature survival data are expected in 2013.
The US Food and Drug Administration (FDA) approved everolimus (Afinitor) based on the BOLERO-2 trial. The drug provides a new option for these previously treated patients who have limited treatment options otherwise. While many patients initially respond to aromatase inhibitors, all eventually relapse due to acquired resistance. Other current treatment options are other types of aromatase inhibitors as well as estrogen-receptor antagonists such as fulvestrant and tamoxifen.
“I use everolimus in combination with exemestane in patients whose disease has progressed or demonstrated resistance to a nonsteroidal aromatase inhibitor. I think that oncologists are now beginning to incorporate everolimus into this setting,” said Sara Hurvitz, MD, medical oncologist at the University of California in Los Angeles.