Harold J. Burstein, MD, PhD
Adjuvant endocrine therapy alone is noninferior to adjuvant chemoendocrine therapy in patients with hormone receptor (HR)–positive, HER2-negative, node-negative early-stage breast cancer who have an intermediate risk of distant recurrence based on the Oncotype DX Breast Recurrence Score test, according to results from the phase III TAILORx study.
The results, presented at the 2018 ASCO Annual Meeting,1
are expected to save thousands of women from overtreatment with chemotherapy. The noninferiority of endocrine therapy alone compared with endocrine therapy plus chemotherapy (HR = 1.08; 95% CI, 0.94-1.24; P
= .26) met the trial’s primary endpoint.
“These are very important data because this is the most common form of breast cancer in the United States and developed countries, and the most challenging decision we make with these patients is whether or not to recommend adjuvant chemotherapy with all of its side effects and with its potential benefits,” said ASCO expert Harold A. Burstein, MD, PhD, of the Dana-Farber Cancer Institute following the presentation. “What the data provided here today from this massive NCI-sponsored trial show is that the vast majority of women who have this test performed on their tumor can be told that they don’t need chemotherapy, and that can be said with tremendous confidence and reassurance.”
Estrogen receptor (ER)–positive, HER2-negative, node-negative breast cancer is one of the most common types of breast cancer, accounting for up to 50% of breast cancers, noted lead study author Joseph A. Sparano, MD, the associate director for clinical research at the Albert Einstein Cancer Center. Up to 30% of patients with these tumors typically have a recurrence by 10 years. Although adjuvant chemotherapy is recommended for these patients, the benefit is typically small, on the order of 3% to 5%.
The 21-tumor gene expression assay, Oncotype DX, helps to predict the need for chemotherapy based on patient scores from 0 to 100. Patients with a score of 26 to 100 benefit from the use of added chemotherapy to endocrine therapy, while those with a low risk of recurrence (0-10) derive minimal to no benefit from added chemotherapy. The benefit of added chemotherapy has been uncertain for patients with intermediate risk (11-25).2
TAILORx is a phase III randomized, prospective, noninferiority trial that included women with ER-positive, HER2-negative, node-negative breast cancer who met criteria for adjuvant chemotherapy. Between April 2006 and October 2010, 10,273 women were registered for the study.
“[This is] the largest adjuvant breast cancer trial ever performed. It was performed in 6 countries, 4 continents, over 1100 sites…and includes a total of 30 co-authors,” said Sparano, who also serves as the vice chair of the ECOG-ACRIN Research Group, which designed and conducted the study.
The women were divided into different arms based on their recurrence score. Those with a low recurrence score of 0 to 10 (n = 1629 evaluable patients) were included in arm A and received endocrine therapy alone. Women with a high recurrence score of 26 to 100 (n = 1389 evaluable patients) were enrolled in arm D to receive endocrine therapy in combination with standard adjuvant chemotherapy.
Of 6711 evaluable women with an intermediate recurrence score of 11 to 25, 3399 were randomized to receive endocrine therapy alone, and 3312 were randomized to the standard treatment arm to receive endocrine therapy plus chemotherapy. Randomization was based on stratification factors of menopausal status, planned chemotherapy, planned radiation, and recurrence score groupings of 11 to 15, 16 to 20, and 21 to 25.
Sparano added that the mid-range recurrence score randomized arms were originally based on a recurrence score of 18 to 30 that was later changed to 11 to 25 to account for exclusion of higher-risk patients with HER2-positive disease and to minimize the potential for undertreatment.
Importantly, Sparano highlighted that the trial was a prospective study reflecting current standards for modern chemotherapy and endocrine therapy. Burstein added after the presentation that prior studies employing the 21-gene recurrence score test were based on older standards of chemotherapy. These findings helped to validate the role of adjuvant endocrine therapy with or without chemotherapy in the setting of modern chemotherapy regimens.
The median age of the participants was 55 years with 33% being aged 50 or younger. More than half of the patients (57%) had intermediate-grade disease and 63% had a 1-2 cm tumor.