ASCO 2018-TAILORX-CHEMOTHERAPY NOT NEEDED FOR MOST PATIENTS WITH EARLY BREAST CANCER

Adjuvant chemotherapy is not necessary for a large proportion of women with early-stage breast cancer, according to new findings that experts agree are "practice changing."

The results come from a federally funded study, the Trial Assigning IndividuaLized Options for TReatment (TAILORx), which involved more than 10,000 patients and tested the 21-tumor gene expression assay (Oncotype Dx, Genomic Health).

"This is the largest adjuvant breast cancer trial ever performed," said lead study author Joseph A. Sparano, MD, associate director for clinical research at the Albert Einstein Cancer Center and Montefiore Health System in New York City and vice-chair of the ECOG-ACRIN Cancer Research Group.

"What we were really trying to do with this trial was 'thread the needle,'" he said.

"In terms of the big picture and the impact on care, application of this test in clinical practice in this population will spare an estimated 70% [of patients] and limit chemotherapy to the 30% who may benefit from it," he added.

The results showed that about 70% of patients with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, axillary node–negative early-stage breast cancer, who received a midrange (intermediate) score on the Oncotype Dx test, could be spared chemotherapy. The trial found no difference in the disease-free survival whether these women were treated with endocrine therapy alone or with the combination of endocrine therapy with chemotherapy.

The results were presented during the Plenary Session here at the American Society of Clinical Oncology (ASCO) 2018 and simultaneously published in the New England Journal of Medicine.

Undetermined Benefit

About half of all breast cancers are hormone receptor positive, HER2 negative, and axillary node negative (ie, like the trial population), but up to 30% of patients have incurable recurrences by 10 years, Sparano explained.

Adjuvant chemotherapy is typically recommended to reduce this risk for relapse, but the absolute benefit is small (3% to 5%). "This results in many women being overtreated, because endocrine therapy would be adequate," he explained.

Oncotype DX is a commercially available gene-expression assay that provides prognostic information in hormone receptor–positive breast cancer, with a  recurrence score that ranges from 0 to 100.

Patients who obtain a high score (defined as 26 or higher, or sometimes as 39 or higher) are considered to be at high risk for relapse and so are considered to benefit from chemotherapy.  

Patients who obtain a low score (0 to 10) are considered to have a very low rate of distant recurrence (2% at 10 years), and that recurrence is not likely to be affected with use of adjuvant chemotherapy. Thus, these women can skip it.

However, for the patients who score in the midrange between these two extremes — about two thirds who undergo testing — whether chemotherapy would reduce the risk for recurrence has been unclear.  

So this is what the new trial set out to investigate.

No Benefit for Most Patients 

The study enrolled 10,273 women with hormone receptor–positive, HER2-negative, axillary node–negative breast cancer, and of this group, 6711 had a midrange recurrence score of 11 to 25.

They were randomly assigned to receive endocrine therapy alone or endocrine therapy and chemotherapy.

At the final analysis, with a median follow-up of 90 months, there were 836 events of invasive disease recurrence, second primary cancer, or death. This included 338 (40.4%) recurrences of breast cancer as the first event, of which 199 (23.8% of the total events) were distant recurrences.

Overall, endocrine therapy was noninferior to chemotherapy plus endocrine therapy, with a hazard ratio (HR) for invasive disease recurrence, second primary cancer, or death of 1.08 (endocrine vs combination therapy; 95% confidence interval [CI], 0.94 - 1.24; P = .26).

Similarly, endocrine therapy alone was also noninferior for other endpoints that included freedom from recurrence of breast cancer at a distant site (HR for recurrence, 1.10; P = .48), freedom from recurrence of breast cancer at a distant or local-regional site (HR for recurrence, 1.11; P = .33), and overall survival (HR for death, 0.99; P = .89).