Updated data from the CHiRP study demonstrates clinical potential with the RaDaR minimal residual disease test in patients with high-risk hormone receptor–positive human epidermal growth factor receptor 2-negative breast cancer.
The RaDaR minimal residual disease (MRD) test, a highly sensitive liquid biopsy assay, has shown clinical potential in patients with high-risk hormone receptor (HR)–positive, human epidermal growth factor receptor 2-negative breast cancer, according to Inivata.1
These updated data come from the CHiRP study which aimed to examine the prevalence and dynamics of circulating tumor DNA (ctDNA) and its association with metastatic recurrence in patients with high-risk early-stage HR-positive, HER2-negative breast cancer at least 5 years from the time of diagnosis.
“To our knowledge, this is the first data to be released on plasma ctDNA analysis for MRD detection in late adjuvant HR-positive breast cancer patients, building on our existing evidence base in breast cancer as well as other indications. These results support the potential benefits of the clinical utility of the RaDaR assay in improving patient outcomes,” said David Eberhard MD PhD, chief medical officer of Inivata, in the press release. “The data will be useful in informing the future study of liquid biopsy to personalize treatment and prevent, or delay, late recurrence of early-stage breast cancer.”
In the prospective CHiRP study, a total of 103 patients with high-risk stage II-III HR-positive BC who were diagnosed more than 5 years prior without clinical evidence of recurrence were enrolled.
The RaDaR assay was used in the study and works by using patient-specific primer panels to analyze ctDNA in blood samples that were collected every 6-12 months. These samples began to be collected at a median time of 8.4 years (range, 4.9-20) after initial diagnosis and were followed for clinical tumor recurrence. Median follow-up time was 2 years from the first blood sample. Whole-exome sequencing was performed on the primary tumor tissue of patients in order to identify somatic mutations tracked by a personalized, tumor-informed ctDNA test to detect MRD.
Among the 103 patients enrolled, 85 had sufficient tumor tissue with all but 2 of these patients (97.6%) showing successful whole-exome sequencing. Of the 83 who comprised the analytic cohort, patients had a median age of 53 years (range, 29-71) at initial diagnosis and all were female. The majority of patients (n=57; 68.7%) had stage III disease, and most (75, 90.4%) received chemotherapy. Seventeen of the 75 patients who received chemotherapy (22.7%) had neoadjuvant chemotherapy while 58 of 75 (77.3%) had adjuvant chemotherapy.
There were 32 patients (38.6%) enrolled who had breast conserving surgery and radiation while 51 (61.4%) had mastectomy. A total of 46 of 51 (90%) who had mastectomy also had radiation therapy, and all patients in this cohort received ET. Thirty-eight (45.8%) remained on adjuvant ET by the time of the last follow-up. Forty-two of the 45 patients who had completed adjuvant ET (93.3%) received more than 5 years of treatment.
Further, the median clinical follow-up was 10.4 years (range, 6.7-22.8) from the first plasma sample collected on study, the diagnosis was 2 years (range, 0-3.9). Additionally, personalized ctDNA assays were designed to target a median of 36 variants which tested 219 plasma samples.
Findings showed that the median time from diagnosis to first sample was 8.4 years, and the median follow-up was 10.4 years from diagnosis and 2 years from the first sample. Per patient, the median number of plasma samples was 2.
There were 8 patients (10%) who had positive MRD testing at any time point, and 6 patients (7.2%) who developed distant metastatic recurrence with median ctDNA lead time of 12.4 months. All 6 of the patients who developed distant metastatic recurrence were MRD-positive before overt clinical recurrence.
One patient (1.2%) had only a 2-day lead time, had not had blood collection in the preceding 567 days, and did not show MRD to be identified with local recurrence. Additionally, 2 of the 8 MRD-positive patients had not had clinical recurrence at last follow-up. At the time of diagnosis, both of these patients had stage IIIC disease and did not have restaging scans since initial diagnosis.
Overall, findings from the CHiRP study showed that among patients with high-risk HR-positive breast cancer in the late adjuvant setting, ctDNA was identified at a median of 1 year prior to cases of distant metastasis. These data are consistent with studies of late recurrence in HR-postive breast cancer which show the annual rate of late recurrence in the highest risk group to be between 1.7% and 4.5% per year.
There are multiple ongoing clinical trials currently underway investigating the efficacy of potential interventions after MRD detection, including TRAK-ER (NCT04985266), DARE (NCT04567420), and LEADER (NCT03285412) trials. Future studies are expected to examine ctDNA-guided intervention to determine whether or not it can alter clinical outcomes in patients with HR+ breast cancer.
“The results of the CHiRP study mark an important step in helping us understand the baseline prevalence and role of ctDNA in the late adjuvant setting of HR-positive breast cancer. The data demonstrate how important targeting multiple variants using an individualized assay, such as the RaDaR assay, can be in identifying MRD-positive patients. It is exciting to see this data highlighting the promise of this method and I am hopeful that, with further studies, earlier detection of disease may enable earlier intervention and more positive outcomes for patients at greater risk,” added Marla Lipsyc-Sharf, MD, clinical oncology fellow at the Dana-Farber Cancer Institute, in the press release.