THE HIGHLY ANTICIPATED results of the phase III TAILORx study are in—and they indicate that the vast majority of patients with “intermediate-risk” early-stage breast cancer can forgo chemotherapy. 

Joseph A. Sparano, MD

“Our study shows that chemotherapy may be avoided in about 70% of women with hormone receptor–positive, HER2-negative, and axillary node–negative breast cancer who would otherwise be candidates for recommending or at least considering therapy based on clinicopathologic features,” said Joseph A. Sparano, MD, who reported the findings of TAILORx at the 2018 ASCO Annual Meeting Plenary Session.¹ Dr. Sparano is Associate Director for Clinical Research at the Albert Einstein Cancer Center and Montefiore Health System in New York, and Vice-Chair of the ECOG-ACRIN Cancer Research Group. The findings were simultaneously published in The New England Journal of Medicine.² 

‘Threading the Needle’ 

TAILORx (Trial Assigning Individualized Options for Treatment) evaluated whether women with midrange recurrence scores of 11 to 25 on the 21-gene Oncotype DX assay may be spared chemotherapy or can be treated as effectively with endocrine therapy alone. Women with a low score (0–10) typically were assigned to receive only hormone therapy, and those with high scores (26–100) receive hormone therapy plus chemotherapy based on results of prior validation studies. At the time the study was designed and conducted, however, there was uncertainty as to whether chemotherapy was beneficial for about two-thirds of women who had a midrange recurrence score and met clinical criteria for recommending or considering chemotherapy. 

“With TAILORx, we were really trying to ‘thread the needle,’” Dr. Sparano said at a press briefing. The recurrence score had proven to be as prognostic for recurrence as other gene expressions but had also been shown to be predictive of chemotherapy benefit if high, which is one of the major reasons why it was selected for TAILORx. “We can now approach the care of patients with early-stage breast cancer with an unprecedented level of precision and evidence,” he said. 

“Chemotherapy may be avoided in about 70% of women with hormone receptor–positive, HER2-negative, and axillary node–negative breast cancer.”

— Joseph A. Sparano, MD

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The question has been how to manage those roughly two-thirds of patients with intermediate-range scores where there was, as he put it, “therapeutic equipoise.” TAILORx has answered that question, according to multiple breast cancer experts. 

Harold J. Burstein, MD, PhD, FASCO, Associate Professor of Medicine at Harvard Medical School, commented at a press briefing, “The most challenging decision we make in these patients is whether or not to recommend chemotherapy. There’s a huge difference between telling a patient, ‘You may benefit a little bit,’ vs saying, ‘There’s no benefit for you.’” 

Harold J. Burstein, MD, PhD, FASCO

He continued, “The data provided here … show that the vast majority of women who have this test can be told they don’t need chemotherapy, with tremendous confidence and reassurance. These are extraordinary data that allow us to individualize treatment, based on extraordinary science that now has prospective validation.” 

TAILORx Details 

TAILORx ENROLLED 10,273 women with hormone receptor–positive, HER2-negative, axillary node–negative breast cancer. Of them, 6,711 had recurrence scores of 11 to 25 and were the subject of this analysis. Patients had tumors that were 1.1 to 5.0 cm, or 0.6 to 1.0 cm if they were intermediate- or high-grade. All were treated with a taxane- or anthracycline-containing regimen, 90% of postmenopausal women received aromatase inhibitors, and 15% of the premenopausal group underwent ovarian suppression. 

The 6,711 women with recurrence scores indicating an intermediate risk for recurrence (11–25) were randomly assigned to receive endocrine therapy alone or endocrine therapy plus chemotherapy. The primary endpoint was invasive disease–free survival. The trial was designed to show noninferiority for endocrine therapy alone by not rejecting equality (hazard ratio [HR] margin up to 1.322 for omission of chemotherapy). The final analysis was based on 836 invasive disease–free survival events, after a median follow-up of 7.5 years. 

The study met its primary endpoint, showing noninferiority (HR = 1.08, P = .26) in the intention-to-treat population. Endocrine therapy was also noninferior for distant recurrence–free interval (HR = 1.10, P = .48), recurrence-free interval (HR = 1.11, P = .33), and overall survival (HR = 0.99, P = .89). 

The invasive disease–free survival rates at 9 years were 83.3% for endocrine therapy alone vs 84.3% for endocrine therapy plus chemotherapy. Similarly, distant recurrence–free survival rates were 94.5% and 95.0%, and overall survival rates were 93.9% and 93.8%, respectively. 

TailoRx also confirmed earlier findings for the high- and low-risk groups. Women with recurrence scores of 0 to 10 had only a 3% rate of distant recurrences with endocrine therapy alone, whereas those with recurrence scores of 26 to 100 had a 13% risk despite receiving chemotherapy plus endocrine therapy. 

In an exploratory analysis of the 2,216 women ≤ 50 years old, the following findings were made regarding the potential chemotherapy benefit by recurrence scores in this younger subset: 

• Recurrence scores 16 to 20: 9% fewer invasive disease–free survival events with chemotherapy, including 2% fewer distant recurrences 
• Recurrence scores 21 to 25: 6% fewer invasive disease–free survival events with chemotherapy, mainly consisting of fewer distant recurrences 
• Recurrence scores 0 to 15: 3% distant recurrence rate with endocrine therapy alone 
• Recurrence scores 11 to 15: no evidence of chemotherapy benefit. 

In brief, the findings suggest that for women with hormone receptor–positive, HER2-negative, node-negative early breast cancer, chemotherapy can be avoided in all woman > 50 years old with recurrence scores of 0 to 25 and in all women aged ≤ 50 with recurrence scores of 0 to 15. In younger patients, there is some chemotherapy benefit for those with recurrence scores of 16 to 25, but endocrine therapy alone yields a good prognosis for those with recurrence scores of 0 to 15, Dr. Sparano said. ■

DISCLOSURE: Dr. Sparano has been a consultant/advisor for Genentech/Roche, Novartis, AstraZeneca, Celgene, Lilly, Celldex, Pfizer, Prescient Therapeutics, Juno Therapeutics, and Merrimack; has stock and other ownership interests with MetaStat; and has received institutional research funding from Prescient Therapeutics, Deciphera, Genentech/Roche, Merck, Novartis, and Merrimack. Dr. Burstein reported no conflicts of interest. 

REFERENCES 

1. Sparano JA, Gray RJ, Wood WC, et al: TAILORx. 2018 ASCO Annual Meeting. Abstract LBA1. Presented June 3, 2018. 

2. Sparano JA, Gray RJ, Makower DF, et al: Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. June 3, 2018 (early release online).