The combined analysis of two phase III clinical trials shows that exemestane, an aromatase inhibitor (AI), may better prevent breast cancer recurrence in women with early-stage hormone receptor–positive breast cancer, as compared with tamoxifen. The results of the Tamoxifen and Exemestane Trial (TEXT) and the Suppression of Ovarian Function Trial (SOFT) show that combining exemestane with ovarian function suppression (OFS) in premenopausal breast cancer patients who have hormone-sensitive disease results in a reduction in the risk of breast cancer recurrence by 34%, compared with treatment with tamoxifen in combination with OFS.
At a median of 5.7 years of follow-up, the patients on an exemestane regimen had a 28% reduced risk of having invasive disease (P = .0002). Disease-free survival (DFS) was 91.1% in the exemestane arm compared with 87.3% in the tamoxifen arm.
The results (abstract LBA1) were presented at the plenary session by study author Olivia Pagani, MD, of the Oncology Institute of Southern Switzerland in Bellinzona, Switzerland, at the American Society of Clinical Oncology Annual Meeting, held May 30–June 3 in Chicago.
“Our study shows that adjuvant therapy with exemestane plus ovarian suppression significantly reduces the risk of recurrence compared to tamoxifen plus ovarian suppression,” said Pagani during the session.
The 5-year overall survival rates were over 95% for both study groups. Longer-term follow-up is still needed to assess overall survival, as well as long-term toxicities and effects on fertility.
Tamoxifen is currently the standard adjuvant therapy for women with early-stage breast cancer and is used for prevention of recurrence in those with hormone-sensitive disease. Although OFS is sometimes added to a tamoxifen regimen in higher-risk patients in other countries, the combination is rarely used in the United States because the added therapy has not been proven to add benefit. The SOFT trial is also addressing whether this combination is beneficial for patients, with results to be disclosed sometime later this year.
AIs have primarily been used to treat postmenopausal, rather than premenopausal, women with breast cancer. Because the use of AIs requires low estrogen levels, the therapy was combined with OFS to mimic the lower hormone levels of postmenopausal women.
The two trials followed a total of 4,690 women that were randomized to either exemestane or tamoxifen with OFS for 5 years. The SOFT trial randomized 3,066 women, and the TEXT trial randomized 2,672 women. The median age of the women in the trial was 43 years.
The drug triptorelin, surgical oophorectomy, or ovarian irradiation was used to achieve OFS. Some of the patients also received adjuvant chemotherapy, as deemed necessary by their oncologists.
Fourteen percent of trial participants discontinued their therapies early, resulting in a rate of adherence that is greater than the rate seen in regular clinical practice, according to Pagani. Rates of high-grade adverse events were similar in both treatment arms (31% and 29% in the exemestane and tamoxifen arms, respectively) and similar to previously reported studies.
As 43% of patients did not receive chemotherapy in addition to endocrine therapy, Dr. Pagani stated that the results of these trials “indicate that some premenopausal women with hormone-positive breast cancer may have excellent prognosis when treated with 5 years of adjuvant endocrine therapy without chemotherapy.”
The phase III trials were coordinated by the International Breast Cancer Study Group, along with the Breast International Group and the North American Breast Cancer Group; patients from 27 countries were recruited. The studies were also partially funded by the National Cancer Institute.