According to research recently published in The New England Journal of Medicine, chemotherapy is not more beneficial than treatment with hormone therapy alone for women with hormone receptive (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and axillary node-negative breast cancer. The data were also presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.
The Trial Assigning Individualized Options for Treatment (TAILORx) was designed to address knowledge gaps by determining whether chemotherapy is beneficial for women with a mid-range recurrence score of 11 to 25 in the 21-gene recurrence-score assay. The recurrence score based on the assay ranges from 0 to 100 and is predictive of chemotherapy benefit when the score is high (26 or above). When the score is low (0-10), it is predictive of a low rate of recurrence (2%) at 10 years that is not likely to be affected by adjuvant chemotherapy. Secondary objectives of the trial included prospectively confirming that a low recurrence score of 0 to 10 is associated with a low rate of distant recurrence when patients are treated with endocrine therapy alone.
A total of 10273 women aged 18 to 75 who had HR-positive were enrolled in the study between April 2006 and October 2010. The participants were assigned to one of four treatment groups based on their assay score. Women with a recurrence score of 10 or lower were assigned to receive endocrine therapy only and women with a recurrence score of 26 or higher were assigned to receive chemotherapy plus endocrine (chemoendocrine) therapy. Women who scored between 11 and 25 were randomized to receive either endocrine therapy alone or chemoendocrine therapy. Among the 9719 eligible patients with follow-up information, 6711 (69%) had a recurrence score of 11 to 25, 1619 (17%) had a recurrence score of 10 or lower, and 1389 (14%) had a recurrence score of 26 or higher. For the mid-range cohort, the median duration of follow-up was 90 months for invasive disease-free survival (iDFS) and 96 months for overall survival.
For the mid-range group, the median duration of endocrine therapy was 5.4 years. The most commonly prescribed chemotherapy regimens among the randomly assigned patients were docetaxel-cyclophosphamide (56%) and anthracycline-containing regimens (36%). At the time of final analysis, there were 836 events of invasive disease recurrence, second primary cancer, or death. In the intention-to-treat population, endocrine therapy was noninferior to chemoendocrine therapy in the analysis of iDFS (HR for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% CI, 0.94-1.24; P = 0.26). Endocrine therapy was likewise noninferior to chemoendocrine therapy in the analysis of other endpoints, including ratio for recurrence and freedom from recurrence of breast cancer at a distant site (HR for recurrence, 1.10; 95% CI 0.94-1.24; P = 0.26) and overall survival (HR for death, 0.99; P = 0.89).
In the as-treated group, analyses were consistent with those of the intention-to treat (ITT) analyses for iDFS (HR for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.14; 95% CI, 0.99-1.31; P = 0.06), freedom from recurrence of breast cancer at a distant site (HR, 1.03; P = 0.81), and overall survival (HR for death, 0.97; P = 0.78).
The survival rates at 9 years for the ITT population with a recurrence score of 11 to 25 was 93.9% in the endocrine-therapy group and 93.8% in the chemoendocrine-therapy group. Disease-free survival rates at 9 years were 83.3% in the endocrine-therapy group and 84.3% in the chemoendocrine-therapy group. In women aged 50 or younger, chemoendocrine therapy was associated with a lower rate of distant recurrence than endocrine therapy if the recurrence score was between 16 and 20 (0.8% difference at 5 years and 1.6% at 9 years) or 21 to 25 (3.2% difference at 5 years and 6.5% difference at 9 years). When all recurrence-score groups were considered, there were significant differences in the rates of iDFS, recurrence, and death (P < 0.001), which the researcher believe was driven largely by the higher likelihood of having an event in the cohort with a recurrence score of 26 or higher.
Based on the results of the study, the authors suggest that chemotherapy can be avoided in about 70% of women with HR-positive, HER2-negative, and node-negative breast cancer (older than 50 and with a recurrence score of 11 to 25 [45%], any age with a recurrence score of 0 to 10 [16%], and age 50 year or younger with a recurrence score of 11 to 15 [8%]). In the remaining 30% of women with HR-positive, HER2-negative and node-negative breast cancer, chemoendocrine therapy may be considered (any age with a recurrence score of 26 to 100 [17%] and aged 50 or younger with a recurrence score of 16 to 25 [14%]). In addition, chemoendocrine therapy may be of some benefit in premenopausal women and those younger than 50 in the higher part of the intermediate range (16 to 25).