Right Sizing HR-Positive Breast Cancer Adjuvant Therapy With Genomic Risk Stratifying Assays

Kevin Kalinsky, MD, MS, Director, Glenn Family Breast Center, Winship Cancer Institute at Emory University, shares his insights on right sizing adjuvant therapy for hormone receptor (HR)-positive breast cancer with the use of genomic risk stratifying assays, a topic he presented at the 2022 GDU Women’s Oncology virtual meeting.

In his presentation, Dr Kalinksy discussed new studies and treatments available to patients with HR-positive breast cancer, such as TAILORx, Responder, the NRG study, and the OFFSET trial.

Transcript:

Hi, I'm Kevin Kalinsky. I'm an Associate Professor of Medicine at Winship Cancer Institute of Emory University, Director of the Glenn Family Breast Center, and I spoke about right-sizing adjuvant therapy in patients with estrogen-driven breast cancer. In this particular field, one of the most significant advances have been the utilization of genomic assays, about tumor-based genomic assays. We spent some time talking about the 3 large, randomized trials: TAILORx, utilizing the 21-gene Oncotype DX Recurrence Score for patients with node-negative breast cancer that was also estrogen-driven and HER2-negative. We spoke about Responder, which also utilized the same assay, but in patients with 1 to 3 positive nodes. And then we talked about Mammoprint, which used the 70-gene assay and looked at discordance between patients based upon their clinical and their genomic risk.

When we focused on TAILORx and Responder, it was really the patients who were less than age 50, who, in an exploratory analysis, we saw that the high clinical risk patients who were 16 to 20 or those who were 21 to 25 in terms of their recurrence score might benefit from the addition of chemotherapy. And in Responder, it was the premenopausal women with recurrent score lessen or equal to 25 who seemed to benefit from chemotherapy.

We talked about some of the limitations that are associated with the studies, including that the rate of ovarian function suppression is limited. About 16% of patients received optimal endocrine therapy. And one of the remaining questions has been, "Well, can we get the same sort of benefit if we just did ovarian function suppression plus hormonal therapy? Do we really need the chemotherapy?" Really asking the question not just whether there's an indirect benefit, meaning that patients stop having their periods, but whether there's a direct benefit as well, meaning is there something underlying in the biology of the tumor, which leads to this differential benefit that we see in pre-menopausal patients.

We also talked about this NRG study that should be opening, hopefully, within the next year called the OFFSET trial, which is a study for this exact population, utilizing the 21-gene Oncotype Recurrence Score for those patients with high clinical risk, recurrence score 16 to 20 or have a recurrence score 21 to 25. This is for the node-negative population, and for the patients who were recurrence score 0 to 25 and have 1 to 3 nodes involved, they will be randomized to receive ovarian function suppression plus an aromatase inhibitor with or without chemotherapy. This study will be a study of about 4000 patients, and this will really help answer the question of whether patients can just do ovarian function suppression plus the hormonal therapy or whether they still need the chemotherapy.

The other thing we talked about in the setting was for the patients who are high clinical risk, the utilization of abemaciclib, based upon the monarchE study. We talked about the FDA label, which is for the patients who have 1 to 3 nodes involved, for instance, with high Ki-67, defined as 20% or greater, and have additional concerning characteristics like a Grade 3 tumor or a tumor that's 5 centimeters or greater.

And we talked about the fact that Ki-67 was prognostic but not predictive, meaning that for those patients who had a high Ki-67, that they had a higher absolute benefit of the addition of Verzenio (abemaciclib) for 2 years, as opposed to those with a lower Ki-67, which still benefited, but just had a lower absolute benefit.

We also talked about where the field is going and the potential utilization of circulating markers like circulating tumor DNA. And we talked about some ongoing studies with oral agents like oral SERDs, selective estrogen receptor downregulators, that are quickly moving into the adjuvant space, either from the beginning, meaning from the time that they're initiating their endocrine therapy, as well as some crossover studies where patients are on endocrine therapy for a couple years and then are randomized to continue that versus switching their endocrine therapy.

We can see that there's a lot that's going on in this space. We talked about the genomic assays. We talked about the utilization of abemaciclib, and we talked about future directions, including the utilization of oral selective estrogen receptor downregulators, and other ways of impacting the estrogen receptor and the potential role of circulating markers.

Thank you for your attention.

Source:

Kalinsky, K. Right Sizing Adjuvant Therapy (Genomic Risk Stratifying Assays). Presented at: Great Debates & Updates in Women’s Oncology. Sep 21-23, 2022. Virtual.