Dr. Joseph A. Sparano
In patients with a recurrence score (RS) of 11 to 25 on the Oncotype DX Breast Recurrence Score assay, chemotherapy did not improve invasive disease–free survival (iDFS) when added to adjuvant ET. Almost two-thirds of the more than 10,000 patients enrolled in the study had a midrange RS of 11 to 25, Joseph A. Sparano, MD, of Montefiore Medical Center, who presented the study results, said.
The study results are expected to be immediately practice-changing, Harold Burstein, MD, PhD, FASCO, of Dana-Farber Cancer Institute, commented during the press conference. “What the data provided here today from this massive
[National Cancer Institute]-sponsored trial show is that the vast majority of women 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 and reassurance,” he said.
Dr. Sparano explained that in ER-positive, HER2-negative, node-negative BC, the gene expression assay has been prognostic for patients with a low RS (0 to 10)—they have a very low risk of recurrence with ET alone. However, patients with a high RS (26 to 100) demonstrated poorer outcomes with higher event rates despite the addition of chemotherapy to ET. But for those with an RS in the midrange (11 to 25)—about two-thirds of those tested—the benefit of adding chemotherapy to ET has been uncertain.
To try to bring clarity to the interpretation of a midrange RS, TAILORx enrolled 10,273 women ages 18 to 75, making this the largest BC treatment trial ever conducted. Patients were assigned to one of four arms: those with an RS of 0 to 10 received ET, those with the midrange RS of 11 to 25 were randomly assigned to either ET alone or ET plus chemotherapy, and those with an RS of 26 to 100 received ET plus chemotherapy. The primary endpoint was iDFS, and the trial was designed to show noninferiority for ET alone.
In those with an RS of 11 to 25, ET alone was noninferior to ET plus chemotherapy (HR 1.08, 95% CI [0.94, 1.24]; p = 0.26). Nine-year iDFS rates were 83.3% for ET and 84.3% for ET plus chemotherapy. In the arms consisting of patients with an RS of 11 to 25, secondary endpoints showed an overall distant recurrence rate of 5% and similar overall survival rates between groups. In the low-RS group, the distant recurrence rate was 3% with ET alone. In the high-RS group, the distant recurrence rate was 13%, despite the addition of chemotherapy.
An exploratory analysis was conducted in the 11 to 25 RS groups to determine whether age had an influence on chemotherapy benefit. The investigators found that, among patients age 50 or younger with a score of 16 to 25, there was some benefit of added chemotherapy; there were 2% fewer distant recurrences for those with an RS of 16 to 20 and 7% fewer for those with an RS of 21 to 25.
The investigators concluded that adjuvant chemotherapy may be spared in all women older than age 50 with an RS of 11 to 25 and in 36% of those age 50 or younger. Of patients aged 50 or younger (14% of the overall population), 64% had an RS of 16 to 25; this subset can derive some benefit from chemotherapy.
“Application of this test in clinical practice in this population could be estimated to spare chemotherapy in 69% and to select chemotherapy in 31%, on average,” Dr. Sparano concluded.
Commenting on the trial, Dr. Burstein added, “The goal of this study was not to just use less treatment. The goal was to tailor treatment. They chose the title very 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.”
–Tim Donald, ELS
*Data based on the press briefing.