Phase 3 TAILORx Results Confirm Chemotherapy Unnecessary in 70% of Women With Early-Stage Breast Cancer

Trial Assigning IndividuaLized Options for Treatment (Rx), or TAILORx, successfully confirmed the benefit of endocrine therapy (ET) alone in patients with early-stage breast cancer who have an Oncotype DX Breast Recurrence Score (RS) of 11 to 25.

The long-awaited results of the TAILORx study, the largest ever breast cancer treatment trial, sponsored by the National Cancer Institute and led by the ECOG-ACRIN Cancer Research Group, were presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting by Joseph A. Sparano, MD, professor of Medicine and Obstetrics, Gynecology, and Women's Health at the Albert Einstein College of Medicine; associate chairman for Clinical Research in the Department of Oncology at Montefiore Medical Center; and associate director for Clinical Research at the Albert Einstein Cancer Center.

The Oncotype DX RS ranges from 0 to 100 and can predict chemotherapy benefit when the score is high, meaning higher than either 26 or 31. A score lower than 10 means the risk of distant recurrence is low, and the women will not benefit from chemotherapy. “The gray area has been the mid-range RS score of 11 to 25—this target population accounts for about 50% of women in the United States,” Soprano said.

The TAILORx trial was designed to help personalize treatment for women 18 to 75 years of age with hormone receptor (HR)-positive, HER2-negative, axillary node (AN)-negative breast cancer whose tumors were 1.1 cm to 5.0 cm in size and who had a mid-range RS. The trial, which enrolled 10,273 women, aimed to clarify whether hormone therapy alone or together with chemotherapy is better for women with an RS of 11 to 25. The trial also wanted to confirm that a low RS of 0 to 10 is associated with a low rate of distant recurrence when patients receive endocrine therapy alone.

A majority (6711, 69%) of the 9719 eligible women had a mid-range RS of 11 to 25 and were randomized to either the chemoendocrine treatment (CET) arm or the endocrine treatment (ET) arm. Women with an RS of 10 or lower (1619, 17%) were in the ET arm and those with a RS of 26 or higher (1389, 14%) were in the CET arm. The primary endpoint was invasive disease-free survival (iDFS), and the trial was designed to show noninferiority for ET alone.

Key secondary end points included freedom from recurrence of breast cancer at a distant site, freedom from recurrence of breast cancer at a distant or local—regional site, and overall survival (OS).

At a median follow-up of 90 months (7.6 months), there were 836 iDFS events at final analysis. ET was noninferior to CET for iDFS (hazard ratio [HR], 1.08; 95% CI, 0.94, 1.24; P = .26) in the intention-to-treat (ITT) population. ET was also noninferior for distant recurrence-free interval (DRFI; HR, 1.03; P = .80), recurrence-free interval (RFI; HR 1.12; P = .28), and OS (HR, 0.97; P = .80).

Nine-year rates were similar for iDFS (83.3% vs 84.3%), DRFI (94.5% vs 95.0%), RFI (92.2% vs 92.9%), and OS (93.9% vs 93.8%) for the RS 11 to 25 arm. The overall recurrence rate was 5%. The study found 3% distant recurrence with ET alone in the RS 0 to 10 arm and 13% distant recurrence with CET in the RS 26 to 100 arm.

The study observed a potential chemotherapy benefit in younger women (≤50 years) with an RS of 16-25, while RS 0 to 15 had good prognosis with endocrine therapy.

Sparano concluded that in women with HR-positive, HER2-negative, AN-negative breast cancer who had a RS of 11 to 25, adjuvant ET was not inferior to CET in the ITT analysis. However, recurrence was high in the RS 26 to 100 arm despite adjuvant CET.

Chemotherapy did benefit women younger than 50 who had a RS between 15 to 25.

“Chemotherapy should be used with caution in this [RS 11 to 25] subgroup with a shared decision-making process for deciding the treatment path,” Soprano concluded.

“The results of our trial suggest that the 21-gene assay may identify up to 85% of women with early breast cancer who can be spared adjuvant chemotherapy, especially those who are older than 50 years of age and have a recurrence score of 25 or lower, as well as women 50 years of age or younger with a recurrence score of 15 or lower,” the accompanying paper that was published in the New England Journal of Medicine concluded.

Reference

Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer [published online June 3, 2018]. N Engl J Med. doi: 10.1056/NEJMoa1804710.