As a third-year fellow, soon to become an academic breast cancer oncologist, this year’s American Society of Clinical Oncology (ASCO) annual meeting was especially exciting. Two of the four plenary session abstracts were breast cancer trials, both from cooperative groups and made possible by government funding. The first abstract is potentially practice changing; the second abstract presented disappointing, negative results from a long-awaited trial.
The TEXT/SOFT Trials
Although the standard treatment for premenopausal women with early-stage, hormone receptor–positive (HR-positive) breast cancer is 5 to 10 years of tamoxifen (Tam), the optimal adjuvant endocrine therapy is uncertain. In postmenopausal women, aromatase inhibitors (AIs) are more effective than Tam, so it makes sense to ask if the same benefit would hold true in premenopausal women. AIs must be given with concurrent ovarian function suppression (OFS) in premenopausal women, therefore the TEXT and SOFT trials were designed to evaluate whether AI plus OFS was better than Tam plus OFS (Tam+OFS). The question of whether Tam+OFS is better than Tam alone was also addressed in the SOFT trial, but those results will not be available until later this year.
TEXT and SOFT, both international, phase 3 trials, randomly assigned premenopausal women with HR-positive, early-stage breast cancer to either exemestane (E) plus OFS (E+OFS) or Tam+OFS. Chemotherapy was optional (at the discretion of the physician) and given concurrent with OFS. The majority of patients received medical OFS with monthly injections of triptorelin. After a median follow-up of 5.7 years, patients in the E+OFS group had significantly improved disease-free survival (DFS) compared with Tam+OFS. Five-year DFS improved from 87.3% with Tam+OFS to 91.1% with E+OFS. Similar improvements were seen in breast cancer and distant recurrence-free intervals, but there was no difference in overall survival (OS) at this early follow-up. Adverse events were similar in both groups and were consistent with those expected with each drug and experienced by postmenopausal women.
The authors of TEXT/SOFT concluded that, in premenopausal women with HR-positive early-stage breast cancer, adjuvant treatment with E+OFS reduces the risk of recurrence compared with Tam+OFS. Although this is a potentially practice-changing result, questions still remain, the most important question perhaps being: Is Tam+OFS better than Tam alone? Second, for higher-risk premenopausal patients, the standard of care is now 10 years of Tam rather than 5, based on the results of the ATLAS and ATTOM trials. Therefore, the comparator arm in the TEXT and SOFT trials (5 years of Tam+OFS) was not representative of current practice trends, especially for high-risk women. However, it is unlikely that another similar trial would be conducted evaluating 10 years of Tam plus OFS versus Tam alone or AIs plus OFS, given the decades of follow-up that would be required.