Dr Alexey Aleshin: I-SPY 2 Findings Show How We Can Dynamically Monitor ctDNA

Plasma samples collected from the women in this study—at baseline and during and after neoadjuvant treatment—demonstrate that residual circulating tumor DNA (ctDNA) correlates with a poor prognosis in women with early-stage breast cancer, explained Alexey Aleshin, MD, senior medical director of Oncology at biotech giant Natera, when discussing findings he presented at this year’s San Antonio Breast Cancer Symposium.

Transcript

What did the I-SPY2 trial investigate? What were the desired outcomes?

I-SPY2 was a collaboration between the investigators that conducted that study as well as Natera to look at a cohort of patients on one of the I-SPY2 arms to really ask the question, “Well, can we first of all identify circulating tumor DNA in these patients with early-stage breast cancer and then can we dynamically monitor it over time?”

So in this cohort, there were 4 plasma samples collected throughout the neoadjuvant setting. One plasma sample was collected at treatment initiation, the so-called baseline plasma sample, and then there were 2 plasma samples collected during the course of patients’ neoadjuvant treatment, as well as one after completion of neoadjuvant therapy and before surgery. So in this study, we were able to really show that we can detect ctDNA in a large number of these women and we can also monitor dynamically over time.

I think some of the exciting conclusions from the study were that residual circulating tumor DNA, or persistence of circulating tumor DNA prior to surgery, was associated with a fairly poor prognosis in these women. Really, this was even independent of pathological CR [complete response] status. Additionally, early ctDNA clearance identified a subgroup of women who had better prognoses and were more likely to achieve pathological CR, a so-called surrogate that can be used to really predict an outcome that's likely to occur in the future.

So the I-SPY2 collaboration really looked at the ability to detect ctDNA in patients with early-stage breast cancer, as well as really evaluate the ability to monitor ctDNA levels over time to really see if dynamic changes would be associated with various outcomes. In this data set, 291 plasma samples from 84 women with early-stage breast cancer, enrolled in one of the arms of the I-SPY2 study, were evaluated with the Signatera assay. And ctDNA levels and ctDNA dynamics were then correlated with outcomes, such as disease-free survival and the presence or absence of pathological CR.