At the 2022 San Antonio Breast Cancer Symposium, Arielle Medford, MD, Dana-Farber Cancer Institute, Boston, MA, discusses cell-free DNA monitoring as part of the ongoing phase 2 LEADER trial to investigate the efficacy of adjuvant endocrine therapy with CDK4/6 inhibitor ribociclib for patients with HR-positive, HER2-negative breast cancer.

In Part 1 of the LEADER trial,the ctDNA of enrolled patients was analyzed for evidence of minimal residual disease, as a predictor of relapse. Part 2 will enroll patients with evidence of minimal residual disease to receive adjuvant ribociclib.

Transcript

Hi, I'm Arielle Medford. I'm a senior medical oncology fellow at the Mass General Cancer Center here at San Antonio Breast Cancer Symposium 2022. And I'm very excited to present the cell-free DNA results from part 1 of the LEADER trial, which is a trial that's assessing the efficacy and tolerability of adding adjuvant CDK4/6 inhibitor, ribociclib, to standard-of-care adjuvant endocrine therapy in hormone receptor-positive, HER2-negative breast cancer.

As part of part 1 of this trial, patients also had cell-free DNA assessed for circulating tumor DNA, or ctDNA, and evidence of that in the adjuvant setting without any evidence of recurrence or metastatic disease is called minimal residual disease or MRD. Of the 81 patients that were on the trial, 42 of them had samples that were suitable for ctDNA analysis. In fact, 2 of them had positive ctDNA, both identified on serial testing, and the remaining patients didn't. Most patients had multiple assays that were consistently negative. Interestingly, those were the only 2 patients that experienced a recurrence, both of which were metastatic. The remaining 40 patients, while follow-up is limited, have not had any evidence of metastatic recurrence, and they've had negative ctDNA testing.

Looking more closely into the 2 patients that did have the positive MRD assays, both preceded clinical or radiographic evidence of recurrence by 7 and 8 months for each of those patients. That begs the question on, and it supports a lot of the prior studies that we've seen that have been showing that evidence of MRD, unfortunately, is predictive of a relapse.

CtDNA has a half-life of around 2 hours or less. Evidence is unfortunately quite consistent with risk of recurrence. For that reason, moving forward, part 2 of the LEADER trial is assessing for evidence of MRD, and if positive, patients are then enrolled in the trial where they would have the adjuvant CDK4/6 inhibitor, ribociclib. That will be part 2. The primary endpoint of that study will be ctDNA clearance with secondary analyses on overall outcomes.

We're excited to be able to have this type of data. The most important thing is we want to improve patient care. While it's important for us to be able to assess patients that are at higher risks of recurrence, as was the case with our 2 patients in the study, the next and most important step is what do we do about it? Does the addition of the ribociclib improve patient outcomes who have positive MRD?

I'm looking forward to that next stage of the study moving forward. It's going to be a good presentation with good discussion.

Source:

Medford AJ, Scarpetti L, Niemierko A, et al. “Cell-free DNA monitoring in a phase II study of adjuvant endocrine therapy with CDK 4/6 inhibitor ribociclib for localized HR+/HER2- breast cancer (LEADER).” Presented at San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, Texas. Poster PD17-03