At the 2022 San Antonio Breast Cancer Symposium, Joseph Sparano, MD, Tisch Cancer Institute, New York, presented updated results from the TAILORx trial, examining the efficacy of endocrine therapy alone for patients with ER-positive, HER2-negative, lymph node-negative breast cancer and a recurrence score of 11 to 25.

In this trial, Dr Sparano reported that in this patient population, about two-thirds of the total study population, endocrine therapy alone was found to be noninferior to endocrine therapy plus chemotherapy. Dr Sparano also discussed racial disparities observed in overall outcomes and recurrence risk that could not be explained by differences in the tumor size, grade, recurrent score, treatment received, insurance status, or access to care.

Transcript:

My name is Dr. Joseph Sparano. I'm chief of the division of hematology-oncology at the Icahn School of Medicine at Mount Sinai and the Tisch Cancer Institute in New York.

I'm here at the San Antonio Breast Cancer Symposium where I presented an update of the landmark TAILORx trial. The trial targeted women with estrogen receptor-positive, HER2-negative, lymph node-negative breast cancer, who were candidates for adjuvant systemic chemotherapy to reduce their recurrence risk and whose treatment was guided by the use of the 21 gene Oncotype DX recurrence score. For those patients for whom we had adequate information to guide therapy at the time, those with a low recurrence score of 0 to 10, or those with a high recurrence score of 26 to 100 were immediately guided to either endocrine therapy alone or chemotherapy plus endocrine therapy. At the time that we initiated the trial, we had a high level of evidence that this was the appropriate treatment for those specific patients. They accounted for about one-third of the patients in the study.

The primary study goal, however, was to determine whether chemotherapy was necessary for patients who had a recurrence score of 11 to 25. This accounted for about two-thirds of the study population. We found in patients who were randomly assigned to receive either endocrine therapy alone or chemotherapy plus endocrine therapy, the endocrine therapy alone was noninferior and the chemotherapy was completely unnecessary. With this result, we were able to reduce the indications for chemotherapy to those who truly benefited from it.

In this update of that original analysis, we now had an additional 3.5 years of follow-up. We followed patients out to 11 years, and substantially more patients had recurrence events. We found several things. First and foremost, we found that the primary trial conclusions were unchanged. There was no benefit for adding chemotherapy to endocrine therapy in this particular group.

The second important finding was that with continued time, more patients did unfortunately experience relapse of their cancer and that the late recurrences exceeded the early recurrences. However, overall, the recurrence rates were still low, under 10%. The prognosis overall was good for this group.

The third thing that we found was a confirmation that Black women with this subtype of breast cancer had worse outcomes than white women. This disparity could not be explained by differences in the tumor size, grade, recurrent score, treatment that they received or their insurance status or access to care. In addition, we found that Black women were more prone to recurrence within the first 5 years of diagnosis while they were receiving endocrine therapy, despite the fact that they were just as adherent to endocrine therapy as white women.

This update of the TAILORx trial provides reassuring data regarding the primary conclusions about who we can safely spare chemotherapy. It also provides new information regarding racial disparities and what may be driving racial disparities.

Lastly, one more thing that I didn't previously comment on. We looked at the outcomes specifically in women 50 years or under because there was a small benefit for chemotherapy in that group. We found that that benefit was largely in women who had a recurrent score of 21 to 25 or a recurrent score of 16 to 20 and had a higher clinical risk for recurrence. We're not exactly sure what's driving the recurrence risk in this population. We think it could be due to the fact that women who are premenopausal and receive chemotherapy are experiencing menopause early – that the chemotherapy is inducing early menopause – which we know is a side effect of the chemotherapy. We think that this may be driving the entire benefit. We don't know for sure. In order to address this issue, there is a new large NCI-sponsored trial being run by the NRG that will take patients who fit into that exact category that I described: node negative, recurrent score 21 to 25, or recurrent score 16 to 20 and low clinical risk, or 1 to 3 positive nodes and recurrent score up to 25. Those patients will be randomized to receive chemotherapy plus endocrine therapy or endocrine therapy, including ovarian function suppression, which will bring on menopause earlier plus aromatase inhibitor therapy. And this will be an important trial that will help address that remaining question.

Source:

Sparano J, Gray RJ, Makower D, et al. “Trial Assigning Individualized Options for Treatment (TAILORx): An update including 12-year event rates.” Presented at San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Abstract GS1-05