Reshma Mahtani, DO
Findings of a combined analysis of the TEXT and SOFT studies demonstrated a benefit with the addition of ovarian function suppression in premenopausal women with hormone receptor (HR)-positive breast cancer, but the information, says Reshma L. Mahtani, DO, highlights the importance of longer follow-up.
At a median follow-up of 8 years, the combined analysis confirmed the superiority in disease-free survival, though not overall survival (OS), of adjuvant exemestane plus ovarian function suppression versus tamoxifen with ovarian function suppression.
Though the benefit of ovarian function suppression has been established, its use in combination with tamoxifen or an aromatase inhibitor (AI) results in considerable adverse events (AEs).
“Sometimes you have to step back so you don’t miss seeing the ‘forest for the trees,’” says Mahtani. “We’re trying to extend the time patients have on hormonal therapy, but not at the cost of significant toxicity and quality of life [QoL].”
In an interview during the 2018 OncLive®
State of the Science Summit™ on Breast Cancer, Mahtani, assistant professor of clinical medicine, Sylvester Comprehensive Cancer Center, University of Miami Health System, discussed the use of adjuvant endocrine therapy in premenopausal breast cancers, specifically the use of ovarian function suppression and GnRH agonists, and the expansion of CDK 4/6 inhibitors in practice.
OncLive: Can you provide an overview of your presentation?
My presentation centered around the use of adjuvant endocrine therapy in premenopausal patients; it’s a decision we have to make in clinic quite often. I presented the 8-year follow-up data from the SOFT trial as well as the updated data from the combined analysis of TEXT and SOFT. These presentations were given at the 2017 San Antonio Breast Cancer Symposium, and the information highlights the importance of longer follow-up in patients with HR-positive breast cancer. When the data were initially presented at 5.6 years, there was no difference with the addition of ovarian function suppression to tamoxifen in the overall group. However, the 8-year follow-up data show a benefit with the addition of ovarian function suppression in the overall population.
Can you elaborate on the data backing the TEXT and SOFT trials?
The trial results demonstrate that there is benefit from the addition of ovarian function suppression. We also see the emergence of a survival signal. An improvement in OS is evident in the patients who had received prior chemotherapy. We understand that there is an improvement with the addition of ovarian function suppression, but we also know that the absolute benefits are higher in patients who have higher-risk disease, such as those who are very young and those who require chemotherapy. This underscores the need for individualized patient care.
How do patients generally tolerate ovarian function suppression?
For most premenopausal patients, ovarian function suppression is associated with more AEs. A woman who receives an AI as opposed to tamoxifen experiences issues with joint discomfort, osteoporosis, and libido. When we use ovarian function suppression with either tamoxifen or an AI, we tend to see worsening AEs. We need to make sure that we’re exposing patients to those additional AEs only if there is going to be a benefit.
What was the third trial you presented at this meeting?
The third trial I presented was a pooled analysis of 5 studies that looked at the use of GnRH agonists to help prevent premature ovarian insufficiency and to improve pregnancy rates. The analysis showed a decrease in premature ovarian insufficiency and higher rates of pregnancy with the use of GnRH agonists during chemotherapy.
This is an important issue because young patients may have fertility concerns. Maintaining menstrual cycles and keeping the ability to conceive is an important point for many of these women. Now we have pretty good data that show that we should consider GnRH agonists in young patients who have an interest in conceiving. The use of these agents did not negatively impact other endpoints we looked at, such as disease-free survival and OS.
Can you speak to the potential of CDK 4/6 inhibitors in this space?
CDK 4/6 inhibitors have been a breakthrough therapy for patients with HR-positive metastatic breast cancer. For many years, hormonal therapy was the only option for patients before they needed chemotherapy. Now, we have the good fortune of not only 1 but 3 highly efficacious CDK 4/6 inhibitors, and their toxicities are well managed. We are now starting to look at these agents in different settings, including the adjuvant setting, to see if there is an improvement in outcomes in earlystage breast cancer.