Many women with hormone receptor (HR)–positive, HER2-negative, lymph node-negative breast cancer and mid-range scores on a 21-gene expression assay may be spared possible overtreatment with chemotherapy according to findings presented at the Plenary session of the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held 1 to 5 June in Chicago, USA. They showed similar recurrence and overall survival rates after treatment with adjuvant endocrine therapy as women receiving chemoendocrine therapy. The results are simultaneously published in the New England Journal of Medicine.
Dr Joseph A. Sparano, Montefiore Medical Centre, Bronx, USA presented findings on behalf of the ECOG-ACRIN Research Group, which conducted the phase III randomised, prospective, non-inferiority TAILORx (Trial Assigning Individualized Options for Treatment, NCT00310180) study in women with HR-positive, HER2-negative, node-negative breast cancer. TAILORx enrolled 10,253 women aged 18-75 years of age with tumours from 1.1 to 5.0 cm in size (or 0.6-1.0 cm and intermediate or high grade tumours).
The women were divided into different arms based on their recurrence score, as evaluated using the Oncotype DX 21-gene expression assay, which provides a Recurrence Score (RS) that has been found to be prognostic for distant recurrence, and for low recurrence with endocrine therapy alone if low (RS = 0 to 10), and predictive of chemotherapy benefit if high (RS = 26 or higher). A total of 6711 evaluable women had a mid-range recurrence score of 11 to 25 and were randomised to receive endocrine therapy alone, or to the standard treatment arm to receive endocrine therapy plus chemotherapy.
TAILORx demonstrated non-inferiority of endocrine therapy compared to chemoendocrine therapy in women with intermediate recurrence scores
The primary endpoint was invasive disease-free survival (iDFS), and the trial was designed to show non-inferiority for endocrine therapy alone by not rejecting equality (hazard ratio [HR] margin up to 1.322 for omission of chemotherapy, 1-sided type I error rate 10%, type II error rate 5%).
At a median follow-up of 90 months after 836 iDFS events, the non-inferiority of endocrine therapy alone compared with endocrine therapy plus chemotherapy was demonstrated for iDFS in the intention-to-treat (ITT) population, thus meeting the primary endpoint (hazard ratio [HR] 1.08; 95% confidence interval [CI] 0.94, 1.24; p = 0.26).
At 9-years, results also showed that endocrine therapy alone was non-inferior to chemoendocrine therapy regarding distant recurrence-free interval (DRFI) rates, HR 1.03; p = 0.80, and recurrence-free interval (RFI) rates, HR 1.12, p = 0.28, respectively.
Nine-year iDFS rates were also similar at 83.3% with endocrine therapy compared to 84.3% with chemoendocrine therapy; overall DRFI rates were similar at 94.5% versus 95.0%, as were RFI rates at 92.2% versus 92.9%, and overall survival rates, which were 93.9% versus 93.8%, respectively.
Recurrence accounted for 338 (41.6%) the first iDFS events; of these, 199 (23.8%) were distant recurrences.
Treatment interaction tests were significant for age (iDFS p=0.03; RFI p= 0.02), but not menopause, tumour size, tumour grade, or either continuous recurrence scores or scores ranging from 11 to 15, 16 to 20, or 21 to 25.
Based on results from the TAILORx trial, the investigators were able to conclude that adjuvant endocrine therapy alone was non-inferior to adjuvant chemoendocrine therapy in patients with HR–positive, HER2-negative, node-negative breast cancer who had an intermediate risk of distant recurrence based on the Oncotype DX Breast Recurrence Score test, although some benefit of chemotherapy was found in some women 50 years of age or younger.
Lisa A. Carey of the University of North Carolina Lineberger Comprehensive Cancer Center, who discussed the study findings entitled her talk as a rational decision-making in early breast cancer, level 1 evidence from TailoRx. According to Dr Carey, the study confirms excellent outcome without chemotherapy in very low RS and supports omitting chemotherapy in small node-negative disease with RS up to 25. However, it did not address identification of a group in which no test is needed.
This trial was sponsored by the US National Cancer Institute (NCI), the Breast Cancer Research Foundation (BCRF), and the Komen Foundation.
Sparano JA, Gray RJ, Wood WC, et al. TAILORx: Phase III trial of chemoendocrine therapy versus endocrine therapy alone in hormone receptor-positive, HER2-negative, node-negative breast cancer and an intermediate prognosis 21-gene recurrence score. J Clin Oncol 36, 2018 (suppl; abstr LBA1).
Sparano JA, Gray RJ, Makower DF, et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. NEJM, Published online 3 June 2018. DOI: 10.1056/NEJMoa1804710