Further results support the use of tests to identify which patients with stages II-IV are resectable colorectal cancer Likely to benefit from adjuvant chemotherapy.
Manufactured by Natera Inc., the Signatera assay measures circulating tumor DNA (ctDNA) to assess molecular residual disease (MRD) 4 weeks after surgery.
New results from the GALAXY study show that 4 weeks after surgery, MRD-positive patients (18%) benefited significantly from receiving adjuvant chemotherapy, whereas MRD-negative patients (82%) did not. indicates that it was not.
“There was no significant benefit in MRD-negative patients who received chemotherapy,” commented Natera Chief Medical Officer Alexei Alesin, MBA. “This is very important, and over time, ctDNA therapy-based approaches will determine who receives adjuvant therapy and who does not.”
The current data are based on results from the same study previously presented at the 2022 ASCO Gastrointestinal Cancers Symposium (GICS). Reported by Medscape Medical News At the time. Median follow-up was then 11.4 months.
The current paper presents results with extended follow-up up to 16.7 months and disease-free survival (DFS) assessed at 18 months.
research is publish online Today’s natural medicine.
Future standard of care?
Signatera is already in clinical use in the United States (launched in 2019). “It’s covered by Medicare and the reimbursement is already in place for testing,” Aleshin said.
More than a quarter of the oncologists who see this patient population are already doing the tests, he said. Medscape Medical News“About 90% of patients have early-stage disease, and there have been no recent innovations in that area. It’s about detecting recurrences.”
He noted that the test could also help monitor treatment response in patients receiving immunotherapy. “It is difficult to image whether a patient is responding to immunotherapy, and ctDNA is much better for this purpose,” he said.
Aleshin’s personal belief is that the test will eventually become standard of care. “We have results from other smaller studies, but we need results from larger cohorts to change how we manage cancer.
extended follow up
The current study describes the results of the GALAXY arm of the ongoing CIRCULATE-Japan trial. This trial is one of the largest and most comprehensive prospective studies of MRD testing in resectable colorectal cancer, according to the authors.
Led by Takayuki Yoshino, M.D., National Cancer Center Hospital East, Kashiwa, Japan, the goal of this study was to prospectively examine and build on previously published evidence. The investigators sought to show that postoperative ctDNA positivity (at MRD) is prognostic for disease recurrence in early-stage colorectal cancer, and to explore the impact of postoperative ctDNA on outcome and choice of adjuvant chemotherapy. , and ctDNA and prognosis.
This cohort included 1039 patients with stage II-IV resectable colorectal cancer, of whom 18% (187/1039) were ctDNA positive 4 weeks after surgery, 82% (852/1039) ) were ctDNA negative.
61.4% of ctDNA-positive patients experienced recurrence compared to 9.5% of ctDNA-negative patients (HR, 10.0; P. < .0001). This was extrapolated to 18-month DFS of 38.4% vs. 90.5%, and this trend was observed at all stages.
In a multivariate analysis of DFS in patients with stage II-III disease, ctDNA positivity 4 weeks after surgery was the most important prognostic factor associated with an increased risk of disease recurrence (HR, 10.82; P. < .001), the authors found that all clinicopathologic risk factors traditionally used for staging and prognosis were non-significant, and the data also compared with carcinoembryonic antigen (CEA) values. suggest that ctDNA is more informative.
Of the 187 patients who were ctDNA positive 4 weeks after surgery, ctDNA clearance data were available for 182. Ninety-two of the 182 received adjuvant chemotherapy and the remaining 90 were placed in the observation group.
Adjuvant chemotherapy was associated with a higher estimated cumulative incidence of ctDNA clearance in 68.5% (63/92) of patients by 24 weeks compared with 12.2% (11/90) of patients in the observation group (Adjusted HR, 8.50; P. < .0001). Patients who did not clear ctDNA also had worse DFS (P. < .0001).
Need randomized data
approach from Medscape Medical News In an original comment, Thomas J. George Jr, MD, professor of medicine and director of the Gastrointestinal Oncology Program at the University of Florida Gainesville, said this is a very impressive dataset. Please provide this information to the research community. ”
“We believe this data further informs the use of the presence or absence of circulating tumor DNA after surgical resection of the tumor. colon cancer “as a prognostic marker,” he emphasized. We cannot say with certainty that we can predict whether we will benefit from
These data further support that patients with MRD-positive disease have a higher risk of recurrence, while those with MRD-negative disease have a lower risk of recurrence, Dr. George explained. “But the patients at high risk of recurrence are those who we already know should benefit from offering adjuvant chemotherapy,” he said.
“To translate this information into individualized/precise oncology-level evidence and to confirm that for individual patients, determination of ctDNA status after surgery can predict whether an individual patient will benefit or not. “There is still a need for prospective, randomized, controlled clinical trials. Fortunately, some of these trials are actively underway.”
And Benjamin Weinberg, M.D., Ph.D., associate professor in the Department of Hematology and Oncology at Georgetown University Lombardi Comprehensive Cancer Center in Washington, DC, said the data are very exciting. “I definitely use this in my practice, but I’m still not comfortable with it. [about withholding adjuvant chemotherapy and] We are observing stage III ctDNA-negative patients, but we are also observing stage II patients who respond poorly to chemotherapy. ”
Another caveat, Dr. Weinberg added, was that the trial was not randomized, and some patients had shorter follow-up. “But prospective randomized studies addressing chemotherapy versus observation with ctDNA are underway, so we may have more answers,” he said.
This research was supported by the Japan Agency for Medical Research and Development. As noted in the paper, some of the authors report industry ties. George reports that he is a consultant for Pfizer Oncology and Tempus Labs.
natural medicine. Published online on January 16, 2023. full text
Roxanne Nelson is a registered nurse, award-winning medical writer, contributor to many major news outlets, and a regular contributor to Medscape.
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