Ruta D. Rao, MD, elaborates on the findings of the ABCSG-16, SOFT, and TEXT clinical trials and how they have shaped adjuvant treatment for ER-positive breast cancer.
Ruta D. Rao, MD
Anastrozole has been shown to be an effective aromatase inhibitor (AI) for patients with estrogen receptor (ER)-positive breast cancer, but patients who remain on the therapy for longer than 2 years are at an increased risk of fractures, notes Ruta D. Rao, MD.
Data from the Austrian Breast and Colorectal Cancer Study Group (ABCSG)-16 trial revealed that following 5 years of adjuvant endocrine therapy, women with ER-positive breast cancer should receive no more than 2 years of the hormone-based chemotherapy anastrozole.
“The most common side effects patients experience are thoracalgia, myalgia, and hot flashes. However, the effect on bone density is the one side effect we, as physicians, worry about the most,” Rao explains.
More encouragingly, updated results of the SOFT trial demonstrated that the addition of ovarian suppression in the adjuvant setting benefited patients with premenopausal breast cancer. Likewise, the TEXT trial found that the use of adjuvant exemestane plus ovarian suppression resulted in a 91.1% disease-free survival (DFS) at 5 years.
Ongoing clinical trials are investigating the use of the CDK 4/6 inhibitor palbociclib (Ibrance) in the adjuvant setting as a potential supplement to endocrine therapy.
In an interview during the 2018 OncLive® State of the Science Summit™ on Breast Cancer, Rao, an associate professor at Rush University Medical Center, elaborated on the findings of the ABCSG-16, SOFT, and TEXT clinical trials and how they have shaped adjuvant treatment for ER-positive breast cancer.Rao: I reviewed 3 abstracts that were presented at the 2017 San Antonio Breast Cancer Symposium: the ABCSG-16, SOFT, and TEXT trials. The ABCSG-16 trial addressed the question of therapy duration. The trial accrued more than 3400 women who had completed 5 years of adjuvant endocrine therapy. At the time of enrollment, they were randomized to either 2 or 5 years of anastrozole. There was no difference between the 2 arms in the primary endpoint of DFS. However, there was an increase in fracture rate for the women who took anastrozole for 5 years as opposed to 2 years. The authors of the study concluded that 7 years of total endocrine therapy may be sufficient.The investigators did look at different subgroups to see if specific groups benefited from longer [durations] of therapy. There did not seem to be a difference in response in nodepositive patients and patients who received prior chemotherapy.
On a clinical basis, this should be determined patient by patient. There was a recent publication in the New England Journal of Medicine that looked at the cumulative risk of breast cancer recurrence between years 5 and 20. Some data show that there is a risk of recurrence during those years in patients with small node-negative tumors. This is also something that needs to be discussed with these patients, taking into account tolerability, side effects, and effects on their bone density.The other 2 abstracts really go together; they address the use of endocrine therapy in premenopausal women. The SOFT trial enrolled approximately 3000 patients who were randomized into 1 of 3 arms. Patients were randomized to either tamoxifen, tamoxifen plus ovarian suppression, or exemestane plus ovarian suppression. The analysis compared tamoxifen with tamoxifen plus ovarian suppression and found that there was a significantly improved DFS for these patients. This was especially true in the patients who had received prior chemotherapy.
The third abstract was an update of the combined SOFT and TEXT trials. They compared the tamoxifen-plus-ovarian suppression and the exemestane-plus-ovarian suppression arms from the SOFT and TEXT trials. The trials were combined because the endpoints were identical. They found that adding exemestane to ovarian suppression gave an additional 4% absolute benefit in improving DFS. Both trials are ongoing, and we are awaiting the overall survival data in the arms that showed a benefit in DFS.These trials gave us a lot of additional information about how aggressive to be with premenopausal women and how to take into account the long risk of relapse that ER-positive patients have. We really have to discuss the risk and the potential benefits of extended adjuvant therapy on an individualized basis.The side effects are what we get the most complaints about. These include hot flashes, not being able to sleep at night because of hot flashes, and achiness in their bones, in addition to others. I have even had patients medically stop ovarian suppression because of these side effects.Managing the side effects of these medications. I’ve learned from experience that putting a premenopausal woman into a menopausal situation with ovarian function suppression can result in significant side effects. If we can come up with ways to manage the side effects, we will be much better at getting patients to adhere to their therapy.We have some trials in the ER-positive adjuvant setting looking at targeted therapies, specifically CDK4/6 inhibitors. We know the role of CDK4/6 inhibitors has been established in the metastatic, first-, and second-line settings. The rationale is based on the fact that it’s so beneficial in the metastatic setting. The patients are randomized, depending on which trial, to either 1 or 2 years of a CDK4/6 inhibitor in addition to their endocrine therapy. It’ll be exciting to see if they can add something for patients in the adjuvant setting.
Pagani O, Regan M, Walley B, et al; TEXT and SOFT Investigators; International Breast Cancer Study Group. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014;371(2):107-118. doi: 10.1056/NEJMoa1404037.