A new analysis of the TEXT and SOFT trials examines the absolute effect of exemestane plus ovarian suppression vs tamoxifen across patients with different recurrence risks.
Compared to intermediate- and low-risk patients, premenopausal women with hormone receptor (HR)–positive, HER2-negative breast cancer who have a high recurrence risk had the greatest absolute benefit from treatment with the aromatase inhibitor exemestane plus ovarian function suppression (OFS) compared with tamoxifen monotherapy.
The new analysis, of the TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) clinical trials, examined the absolute effect of both treatments across patients with different recurrence risks and is published in the Journal of Clinical Oncology.
The original results of the pooled trials demonstrated that exemestane when combined with OFS in premenopausal breast cancer patients with hormone-sensitive disease reduced the risk of recurrence by 34% compared to treatment with tamoxifen plus OFS over 5 years.
“This analysis is about refining the interpretation of the overall TEXT and SOFT trial results to aid decision-making for an individual patient,” study author Meredith M. Regan, ScD, associate professor of biostatistics at the Dana-Farber Cancer Institute in Boston, told Cancer Network.
Those women with HR-positive, HER2-negative early breast cancer who had a high risk of recurrence could have a 10% to 15% potential improvement in the 5-year breast cancer–free interval-the primary endpoint of the trial-if treated with the aromatase inhibitor exemestane plus OFS compared with tamoxifen alone.
Current guidelines from the American Society of Clinical Oncology and Cancer Care Ontario suggest that OFS plus an aromatase inhibitor should be considered rather than tamoxifen alone for women with HR-positive breast cancer patients considered to have high risk of recurrence. The new analysis, said Regan, “provides insight that the potential improvement in 5-year freedom from recurrence is on the order of 10 to 15 percentage points, which is quite substantial.”
Within the SOFT trial cohort, those women who remained premenopausal after chemotherapy had an absolute improvement of 5% or more in 5-year breast cancer–free interval with exemestane plus OFS compared with tamoxifen plus OFS or tamoxifen alone. Among women of intermediate to high risk, the absolute benefit was between 10% and 15%. Among the TEXT trial cohort, the highest benefit with an aromatase inhibitor plus OFS was between 5% and 15% compared with tamoxifen alone.
Patients in both trials were grouped by whether or not they had received chemotherapy in conjunction with examestane. In both trials, patients who did not receive chemotherapy had the highest 5-year breast cancer–free interval, 96.1% overall. Within the SOFT cohort of patients who had received chemotherapy, the 5-year breast cancer–free interval was 82.5%. Exemestane plus OFS improved the 5-year breast cancer–free interval by an average of 5.4% compared with tamofixen plus OFS and by 7.4% compared with tamoxifen alone.
Among TEXT patients who had adjuvant chemotherapy and concurrent gonadotropin-releasing hormone analog, the overall 5-year breast cancer–free interval was 89.3%. The average absolute improvement of treatment with exemestane plus OFS compared with tamoxifen plus OFS was 5.8%.
Follow-up of patients in the TEXT and SOFT trials is still ongoing. The authors of the trials plan to provide another update in 2017. “Because HR-positive, early breast cancer has a persistent long-term risk of recurrence, this follow-up is essential to our understanding of benefits and side effects of these treatments,” said Regan.