The LEADER study was one of the first molecular residual disease guided therapeutic interventions in early breast cancer. MRD is molecular residual disease. It’s something that we’re only recently able to detect because of these novel assays that can detect very low levels of circulating tumor DNA. And what we know is that if you detect CT DNA, circulating tumor DNA, in patients that have otherwise undergone curative intent therapy, the chance of the cancer coming back is incredibly high...
The LEADER study was one of the first molecular residual disease guided therapeutic interventions in early breast cancer. MRD is molecular residual disease. It’s something that we’re only recently able to detect because of these novel assays that can detect very low levels of circulating tumor DNA. And what we know is that if you detect CT DNA, circulating tumor DNA, in patients that have otherwise undergone curative intent therapy, the chance of the cancer coming back is incredibly high. And so the design of the LEADER trial was asking, well, if we escalate therapy in the setting of detectable MRD, can we change patient outcomes? And so patients who had completed curative intent therapy for estrogen receptor positive HER2 negative breast cancer, who subsequently had detectable molecular residual disease on endocrine therapy, we added the CDK4-6 inhibitor ribociclib. And after the first year measured the level of CT DNA change and clearance. And that was the initial endpoint, and then patient outcomes being the follow-up endpoint for the LEADER study. So the LEADER trial, what we ended up identifying was that using this initial whole exome sequencing-based MRD assay, we identified roughly 11% of patients had detectable ctDNA. And then importantly, when looking at scans, it is important to distinguish we identified four patients that also had metastatic recurrence. So those are separate treatment pathway from true MRD. And then for the patients that we then enrolled onto the study and gave ribociclib, we found that patients that had lower levels of baseline CT DNA were more likely to experience clearance. An ongoing question is how much of that is drug versus limitations of the assay itself. With these new refined assays, I’m looking forward to reapplying this with these more sensitive assays to understand clearance versus decrease. But regardless, if a patient experienced a decrease or clearance, they had a much longer distant recurrence-free survival compared to patients that didn’t. We’re talking a year and a half versus less than a half a year in terms of time to distant recurrence. So really looking forward to expanding learning from that study and then applying it to future MRD-based interventional studies.
