One of the most important studies presented at ASCO 2018 showed that endocrine therapy alone was noninferior to endocrine therapy plus chemotherapy in women with estrogen receptor–positive, HER2-negative, node-negative early-stage breast cancer and an intermediate risk score (score, 11-25) on the Oncotype DX gene expression assay for breast cancer.
“Application of this test in this population could spare chemotherapy in about 70% of patients and select chemotherapy for about 30%,” said lead investigator of the study, Joseph A. Sparano, MD, Associate Director for Clinical Research, Albert Einstein Cancer Center and Montefiore Health System, Bronx, NY.
The study was published in the New England Journal of Medicine to coincide with the presentation at ASCO (N Engl J Med. 2018;379:111-121).
It is well known that women with a low risk score on Oncotype DX (score, 0-10) can safely forego chemotherapy, and women with a high risk score (score, 26-100) should have chemotherapy in addition to endocrine therapy; however, optimal treatment for the intermediate-risk group (score, 11-25) has been less well defined.
The TAILORx study was designed to determine how best to tailor treatment. “This study was not designed to just use less treatment. It was designed to tailor treatment, with the name chosen aptly, with the idea that some women are going to need more of some type of therapy and less of another, and others will get a different treatment based on the biology of their tumor,” said ASCO Expert Harold J. Burstein, MD, PhD, Breast Oncology Program, Dana-Farber Cancer Institute, Boston, MA. Dr Burstein was not involved in the study.
“What the data provided here today from this massive National Cancer Institute–sponsored trial show is that the vast majority of women [with estrogen receptor–positive, HER2-negative, node-negative early-stage breast cancer] 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 as assurance,” Dr Burstein said.
However, there is a caveat. An exploratory analysis of the trial suggested that younger women (ie, ≤50 years) with an Oncotype DX risk score of 16 to 25 (still in the intermediate range) have some benefit from chemotherapy. “Younger women with risk scores of 16 to 25 should discuss treatment with their oncologist,” Dr Sparano said.
TAILORx enrolled 10,273 women aged 18 to 75 years at more than 1100 sites in 6 countries, making this the largest breast cancer trial to be conducted to date. The patients were assigned to 1 of 4 arms: those with a risk score of 0 to 10 were assigned to endocrine therapy alone; those with midrange risk scores of 11 to 25 were randomized to endocrine therapy alone or to endocrine therapy plus chemotherapy; and those with a risk score of 26 to 100 received endocrine therapy plus chemotherapy. The primary end point was invasive disease-free survival (iDFS), and the study had a noninferiority design.
In those with a midrange risk score, endocrine therapy was noninferior to endocrine therapy plus chemotherapy. The 9-year iDFS rates were 83.3% for endocrine therapy and 84.3% for endocrine therapy plus chemotherapy. The overall distant recurrence rate in the group of patients with a midrange risk score was 5%, and overall survival was similar.
In the low-range risk score group, the distant recurrence rate was 3%. In the high-range risk score group, the distant recurrence rate was 13%, despite the addition of chemotherapy.
An exploratory analysis performed to look at the effect of age on patients in the midrange risk group showed that chemotherapy had some benefit in patients aged ≤50 years with a risk score of 16 to 25 (the higher end of the midrange). When patients with risk scores of 16 to 20 were compared with those who had risk scores of 20 to 25, there were 2% fewer recurrences for patients with scores of 16 to 20 who received chemotherapy in addition to endocrine therapy compared with 7% fewer recurrences in patients with scores of 21 to 25 who received chemotherapy plus endocrine therapy.
The conclusion was that adjuvant chemotherapy may be spared in all women aged >50 years with a risk score of 11 to 25 and in 36% of patients aged ≤50 years (14% of the overall study population). Of patients aged ≤50 years, 64% had a risk score of 16 to 25, and this subset can derive some benefit from chemotherapy.
“This is an extraordinary day for breast cancer doctors and women with breast cancer, because we can individualize therapy for women with early-stage estrogen receptor–positive, HER2-negative, node-negative breast cancer,” Dr Burstein stated. “This is a powerful finding. Ten-year disease-free survival was 87% for those with highest RS [risk score] group. We have made progress!” he said.