Dr Alexey Aleshin: Persistent ctDNA Is Highly Predictive of Disease Outcome

Changes in circulating tumor DNA (ctDNA) are indicative of treatment response in early-stage breast cancer, and its persistence is linked with high chances of both disease recurrence and death, pointed out Alexey Aleshin, MD, senior medical director of Oncology at biotech giant Natera.

Transcript

What do the I-SPY2 trial results suggest about the potential of personalized ctDNA monitoring in early breast cancer treatment?

The results from the I-SPY2 study, I think, were very provocative. We showed that in the majority of women with early-stage breast cancer, we could identify circulating tumor DNA [ctDNA]. I think the exact number was around 73% of women had detectable ctDNA at the T0 stage, at the baseline typing. Furthermore, we could actually monitor those levels over time. And those dynamic changes were related with the path CR [pathologic complete response] status after completion of neoadjuvant therapy. Furthermore, persistence of ctDNA leading into surgery was highly associated with poor outcomes in these women, with very high risks of recurrence as well as death.

Additionally, and I think more importantly, we were able to show that ctDNA dynamics very, very early into the course of treatment—just after 1 cycle of therapy—were highly predictive of the women who are likely to achieve a pathological CR, as well as women who will have a good long-term outcome, really, I think, pointing for the first time the ability of ctDNA to be used as a surrogate, not just for treatment response monitoring, but also for pathological CR status.

How do these results compare with those seen in other cancer types?

I think, excitingly, that the results in breast cancer compare extremely well with many other cancer types, really suggesting that circulating tumor DNA as assessed by ultrasensitive hemo-informed assays of Natera is something that can be more broadly applicable beyond just breast cancer to all patients with solid tumors.

I think the really main takeaways in this field that we've seen over and over, and in some prior published work, is that patients with persistent ctDNA after surgery have close to 100%, if not 100%, risk of recurrence without additional therapy, really suggesting that circulating tumor DNA is identifying the patients that have residual tumor left in their body, even if it cannot be imaged with conventional methods.

Furthermore, in the neoadjuvant setting, we've seen now in both the I-SPY2 study, as well as some of our work in muscle-invasive bladder cancer, that not only can we detect ctDNA, we can monitor it over time and clearance of ctDNA is invariably associated with higher rates of pathological CR as well as improved long-term outcomes.