26 Jun Stage II Colon Cancer: Guardant Health Study Evaluates Predictive Value of Blood Biomarker in Adjuvant Chemotherapy
MedicalResearch.com: What is the background for this study?
Response: Stage II colon cancer is diagnosed in approximately 25% of all colon cancer cases. Oncologists do not have a reliable biomarker to identify patients who do or do benefit from adjuvant chemotherapy for this population of patients. Circulating tumor DNA is shed by tumor cells as they die and harbors somatic mutations which distinguish its DNA from that of normal cells.
Recently, circulating tumor DNA has shown great promise in distinguishing patients with colon cancer (as well as other solid tumors) that do or do not recur after surgery. Here, patients who have detectable circulating tumor DNA – a surrogate for the presence of microscopic, minimal residual disease – inevitably recur, whereas the likelihood of recurrence is much lower for patients who do not have detectable ctDNA.
MedicalResearch.com: What are the main findings?
Response: While prognostically ctDNA serves as an informative biomarker for patients with resected colon cancer across all stages, we do not have any data showing that this approach can be used to identify patients who do or do not benefit from adjuvant chemotherapy. In other words, we do not know the relevance of ctDNA status as a predictive biomarker to demonstrate benefit with adjuvant systemic treatments.
In this NRG GI-005 phase II/III trial, patients with low-risk (T3N0) stage IIA colon cancer who are deemed by their medical oncologist, based on current practices, not to warrant adjuvant chemotherapy are randomized to standard-of care practice (observation) or prospective testing of ctDNA status. For the latter group, patients who are prospectively identified to have detectable ctDNA will receive six months of adjuvant chemotherapy with a fluoropyrimidine/oxaliplatin combination, whereas patients prospectively identified as not having detectable ctDNA will proceed to observation.
The NRG GI-005 trial is the first trial supported by the NCI for any solid tumor to test ctDNA as a predictive biomarker for benefit of adjuvant chemotherapy.
MedicalResearch.com: What should readers take away from your report?
Response: The NCI is partnering with Guardant Health to use the LUNAR-1 assay for ctDNA assessment. In addition to covering the entirety of the genes most commonly mutated for colorectal cancer, this assay also incorporates a validated colorectal cancer-specific methylation profiling which can further distinguish colorectal cancer from methylation profiles of non-malignant cells. We believe that the heightened sensitivity of methylation profiling, in combination with the genomic assessment for somatic mutations, will optimize assay performance required to detect microscopic levels of residual cancer cells (when present).
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: The NRG GI-005 trial is currently enrolling patients with low-risk stage IIA (T3N0) resected colon cancer across the United States, and has been activated in Canada as well.
Any disclosures? N/A
Phase II/III study of circulating tumor DNA as a predictive biomarker in adjuvant chemotherapy in patients with stage II colon cancer: NRG-GI005 (COBRA).
Van K. Morris, Greg Yothers, Scott Kopetz, Samuel A. Jacobs, Peter C. Lucas, Atif Iqbal, Patrick M Boland, Dustin A. Deming, Aaron James Scott, Howard John Lim, Norman Wolmark, Thomas J. George; NRG Oncology, and UT-MD Anderson Cancer Center, Houston, TX; NRG Oncology, and The University of Pittsburgh, Pittsburgh, PA; NRG Oncology and University of Texas MD Anderson Cancer Ctr, Houston, TX; NRG…
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