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SAN ANTONIO -- The benefits of ovarian function suppression (OFS) for premenopausal hormone receptor (HR)-positive breast cancer persist long term, an updated analysis of two randomized trials showed.

After 12 to 13 years of follow-up, the distant metastasis-free survival (DMFS) rates were 88.4% with an aromatase inhibitor (AI) plus OFS and 86.6% with tamoxifen-OFS. The difference translated into a relative 17% reduction in the hazard ratio in favor of the AI strategy (P=0.03). The overall survival (OS) rates were 90% with an AI and 89% with tamoxifen, a nonsignificant difference. Tamoxifen alone, meanwhile, led to a 12-year DMFS rate of 84.8% and a 12-year OS rate of 86.8%.

Low-risk patients who received no chemotherapy had a 12-year OS rate exceeding 95%, regardless of the endocrine strategy, including tamoxifen alone, reported Meredith M. Regan, ScD, of Harvard Medical School and Dana-Farber Cancer Institute in Boston, at the San Antonio Breast Cancer Symposium (SABCS).

"With 12 to 13 years' median follow-up, distant recurrences and deaths from breast cancer continue to occur, and we plan to continue follow-up for 5 more years," said Regan. "Meaningful relative reductions in distant recurrence and death persist with longer follow-up for use of ovarian suppression with either endocrine therapy versus tamoxifen alone. Absolute reductions are more substantial for those at higher risk, on the order of a 10% reduction in death, emphasizing appropriate selection of patients to receive ovarian suppression."

"Notably, for those patients with low clinical-risk features who did not receive chemotherapy, the longer follow-up continues to support the use of tamoxifen alone," she added.

The findings came from an updated analysis of the and randomized trials, which involved a combined total of 5,700 premenopausal women with early HR-positive/HER2-negative breast cancer.

SOFT randomized patients to 5 years of adjuvant tamoxifen alone or to ovarian suppression treatment plus either tamoxifen or the steroidal AI exemestane. TEXT had a similar design but without a single-agent tamoxifen arm. About 2,500 women did not receive chemotherapy. The primary endpoint for both trials was disease-free survival (DFS).

Previously reported results, after 5 and 8 years of follow-up, showed that adding OFS to tamoxifen reduced the risk of distant recurrence and death, and adding OFS to an AI further reduced the risk of distant recurrence but not survival, said Regan. The absolute benefit varied according to a patient's underlying risk of recurrence. Patients with low-risk clinicopathologic features fared well with tamoxifen alone.

The latest update, after 12 years of follow-up in SOFT and 13 in TEXT, showed that 76% of patients remained alive and in follow-up.

In the three-arm SOFT trial, the 12-year DMFS rates were 87.8% with AI-OFS, 86.2% with tamoxifen-OFS, and 84.8% with tamoxifen alone. In a combined analysis of both trials, the 1.8% absolute difference in 12-year DMFS with AI-OFS versus tamoxifen-OFS proved to be statistically significant (HR 0.83, 95% CI 0.70-0.98, P=0.03). The 1% absolute difference in 12-year OS was not statistically significant.

In the subgroup of patients who received no chemotherapy in the SOFT trial, the 12-year DMFS rates were 95.8% with tamoxifen alone, 95.9% with tamoxifen-OFS, and 97.7% with AI-OFS. The 12-year OS rates for the three treatment groups were 95.8%, 95.2%, and 97.1%, respectively.

Patients who received chemotherapy had 12-year DMFS rates of 75.1% with tamoxifen alone, 77.7% with tamoxifen-OFS, and 79.6% with AI-OFS. The 12-year OS rates were 78.9% with single-agent tamoxifen, 83.6% with tamoxifen-OFS, and 82.9% with AI-OFS. The chemotherapy cohorts in TEXT had 12-year DMFS rates of 84.7% with AI-OFS and 82.3% with tamoxifen-OFS. OS rates were 87.0% with the AI and 84.4% with tamoxifen.

A subgroup analysis showed that patients younger than 35 and those who received neoadjuvant chemotherapy prior to enrollment benefited most from OFS. Within those two subgroups, tamoxifen-OFS led to a 10% absolute improvement in 12-year OS versus tamoxifen alone, and the AI-OFS combination increased the absolute difference versus single-agent tamoxifen to 15%.

SABCS invited discussant Anne Blaes, MD, of the University of Minnesota in Minneapolis, said a key takeaway from the updated analysis was the favorable outcomes in low-risk patients who did not require chemotherapy. The data continue to support the superiority of OFS paired with an AI versus tamoxifen, consistent with the earlier analyses of SOFT and TEXT and also consistent with randomized comparisons of AIs and tamoxifen in postmenopausal patients.

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