Τρίτη, 19 Απριλίου 2016

MORE ANALYSIS OF SOFT-TEXT TRIALS

In an analysis of the SOFT and TEXT trials reported in the Journal of Clinical Oncology, Regan et al found that the greatest benefit of adjuvant exemestane in reducing breast cancer recurrence was among women with the highest risk of recurrence on the basis of clinicopathologic characteristics.
Study Details
The TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) studies investigated adjuvant endocrine therapies in premenopausal women with hormone receptor–positive, HER2-negative early breast cancer. The trials showed that 5 years of adjuvant exemestane plus ovarian function suppression produced better outcome vs tamoxifen plus ovarian function suppression or tamoxifen alone; SOFT also showed better outcome with tamoxifen plus ovarian function suppression vs tamoxifen in patients with risk warranting chemotherapy who remained premenopausal after treatment and that tamoxifen alone was appropriate in some premenopausal women.
The analysis included 4,891 women with hormone receptor–positive, HER2-negative disease in the trials, including 1,353 in SOFT and 991 in TEXT who had received no chemotherapy and 1,271 in SOFT who had received prior (neo)adjuvant chemotherapy and 1,276 in TEXT who had received (optional) chemotherapy. The endpoint was breast cancer–free interval. A continuous composite measure of recurrence risk for each patient was determined using a Cox model incorporating age, nodal status, tumor size and grade, and estrogen receptor, progesterone receptor, and Ki67 expression levels.
The chemotherapy cohorts of each study had the greatest proportion of patients in the highest composite risk quartile. Among all patients, 5-year breast cancer–free interval was 90.8%, ranging from 98.6% in the lowest-risk quartile to 77.5% in the highest-risk quartile.
Outcome in SOFT Cohorts
Among SOFT patients who remained premenopausal after chemotherapy, overall 5-year breast cancer–free interval was 82.5%. Average absolute improvements with exemestane plus ovarian function suppression were 5.4% vs tamoxifen plus ovarian function suppression and 7.4% vs tamoxifen alone, with a 2.0% improvement for tamoxifen plus ovarian function suppression vs tamoxifen alone being observed. Benefit was consistently observed across the continuum of risk.
Absolute benefit with exemestane plus ovarian function suppression was smallest (approximately 3%) in subgroups with the lowest risk and with 5-year breast cancer–free interval > 90% in all three treatment groups. Absolute benefit in higher-risk groups ranged from approximately 5% to > 10% to 15% vs tamoxifen alone. Benefit of approximately 5% was observed for tamoxifen plus ovarian function suppression vs tamoxifen in subgroups with higher composite risk, with benefit diminishing at lower composite risk.
In the SOFT cohort who did not receive chemotherapy, which had the lowest composite risk, 5-year breast cancer–free interval was 96.1% overall; outcomes were similar with all endocrine therapies, with absence of a pattern across the risk spectrum, suggesting absence of clinically relevant improvement in breast cancer–free interval with exemestane plus ovarian function suppression or tamoxifen plus ovarian function suppression vs tamoxifen alone (standard of care) in this lower-risk patient cohort.
Outcome in TEXT Cohorts
In the TEXT cohort of patients who received ovarian function suppression but not chemotherapy, 5-year breast cancer–free interval was 96.1% overall, with exemestane plus ovarian function suppression improving 5-year breast cancer–free interval by on average 3.6% vs tamoxifen plus ovarian function suppression.
Improvement in 5-year breast cancer–free interval was approximately 1% in subgroups with the lowest composite risk, with a 5-year breast cancer–free interval consistently ≥ 95% in both treatment groups. In the subgroups with the highest composite risk, exemestane plus ovarian function suppression resulted in an absolute improvement of approximately 10% in breast cancer–free interval vs tamoxifen plus ovarian function suppression; 5-year breast cancer–free interval in this subgroup was ≥ 95%, similar to that in subgroups with a lower composite risk in this cohort who did not receive chemotherapy.
Among TEXT patients initiating adjuvant chemotherapy and concurrent gonadotropin-releasing hormone analog treatment, the overall 5-year breast cancer–free interval was 89.3%, with exemestane plus ovarian function suppression providing an average 5.8% absolute improvement vs tamoxifen plus ovarian function suppression. Benefit was consistently observed across the continuum of risk.
The smallest absolute benefit (approximately 3%) was observed among patients with the lowest composite risk and 5-year breast cancer–free interval of ≥ 95% in both treatment groups. At higher-risk levels, absolute improvements in the 5-year breast cancer–free interval increased from 5% to 15% with increasing risk.
The investigators concluded: “Premenopausal women with hormone receptor–positive, HER2-negative disease and high recurrence risk, as defined by clinicopathologic characteristics, may experience improvement of 10% to 15% in 5-year breast cancer–free interval with exemestane plus ovarian function suppression versus tamoxifen alone. An improvement of at least 5% may be achieved for women at intermediate risk, and improvement is minimal for those at lowest risk.”
The study was supported by the International Breast Cancer Study Group, the National Cancer Institute, Pfizer, and others.
Meredith M. Regan, ScD, of Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.

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