ASCO Expert Perspective
“This is the first study to not only demonstrate the significance of sustained ctDNA clearance, but also that a dynamic change in ctDNA of more than 50% at six months of adjuvant chemotherapy was associated with improved disease-free survival,” said Cathy Eng, MD, FACP, FASCO, ASCO Expert in Gastrointestinal Cancers.
Use of circulating tumor DNA (ctDNA) to monitor and detect molecular residual disease (MRD) in patients following surgery for colorectal cancer.
2,998 patients from Japan and Taiwan
Monitoring ctDNA status in patients who underwent surgery for colorectal cancer may play an important role in the decision-making process for whether a patient will benefit from adjuvant chemotherapy or not. ctDNA may also be used to monitor the effectiveness of treatment in patients who achieve sustained ctDNA-clearance on adjuvant chemotherapy.
ALEXANDRIA, Va. — Following surgery to remove a tumor, patients may have molecular residual disease (MRD), or a small amount of cancer cells that remain in the body but are too small to be detected with imaging. ctDNA, or liquid biopsy, may be used to detect MRD in patients who underwent surgery for colorectal cancer and determine if they will benefit from receiving adjuvant chemotherapy. The research will be presented at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, taking place January 18-20 in San Francisco, California.
About the Study
“Since the current treatment paradigm for post-operative chemotherapy is largely based on the cancer stage and other clinicopathologic risk factors, monitoring ctDNA status with a highly validated assay allows us to develop a personalized treatment plan for each patient,” said lead study author Hiroki Yukami, MD, from the Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University.
In this updated analysis from the GALAXY study, researchers used a blood test that is custom-built based on the somatic variants found in each patient’s tumor tissue to detect ctDNA following surgery (SignateraTM). These variants were then tracked in the patient’s plasma samples during serial blood draws at 1-, 3-, 6-, 9-, 12-, 18-, and 24-months following surgery or until recurrence. Patients also underwent CT scans of the chest, abdomen, and pelvis every 6 months.
The analysis included 2,998 patients; 1,130 patients received adjuvant chemotherapy and 1,868 patients underwent observation. The primary endpoint was disease-free survival (DFS) – the time between the date of surgery and the date of cancer recurrence or death due to any cause.
During the 2-10 weeks window to detect MRD following surgery, ctDNA results were available for 2,860 patients; 369 (2.9%) were ctDNA+ and 2,491 (87.1%) were ctDNA-. Results of this patient population were as follows:
- Patients who were ctDNA+ had significantly inferior DFS compared to patients who were ctDNA-.
- An analysis of ctDNA dynamics from post-op MRD detection to a 6-month time point revealed that patients who remained ctDNA+ were over 5-times more likely to experience a cancer recurrence compared to those who had ctDNA clearance, meaning there was no MRD detected.
- Among the 445 ctDNA+ patients in the full study population, 240 received adjuvant chemotherapy, 66.3% of whom had ctDNA clearance.
- For patients whose ctDNA was positive after surgery, and whose ctDNA turned negative upon chemotherapy treatment, 58% had sustained clearance compared to 42% of patients who eventually returned to ctDNA+ status. Patients with sustained ctDNA clearance had significantly better DFS compared to those who achieved ctDNA clearance temporarily, meaning that ctDNA- turned ctDNA+ (24-month DFS rate; 90.1% vs. 2.3%).
- Among ctDNA+ patients treated with adjuvant chemotherapy, a 50% or greater decrease in ctDNA levels at 6 months was associated with better DFS compared to patients with a <50% decrease or increase in ctDNA levels (24-month DFS rate; 51% vs. 29%).
“These findings may allow us to spare a considerable number of ctDNA- patients the toxicity of chemotherapy without compromising their long-term survival and identify ctDNA+ patients who should receive chemotherapy. Monitoring ctDNA during surveillance allows for early detection of cancer recurrence, which can potentially enable early intervention, improve the chances of a cure, and/or extend survival,” said Yukami.
The authors plan to further validate the use of ctDNA to guide patient management by studying whether the addition of trifluridine/tipiracil compared with placebo in patients with colorectal cancer who are ctDNA+ at any time after surgery. They are also studying the possibility of omitting adjuvant chemotherapy in patients with colorectal cancer who are ctDNA- during the window to detect MRD following surgery.
This research was funded by the Japan Agency for Medical Research and Development.
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View the News Planning Team disclosures: https://old-prod.asco.org/sites/new-www.asco.org/files/content-files/about-asco/pdf/2024-asco-gi-npt-disclosures.pdf
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