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Expert Point of View: Michael J. Overman, MD


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The study’s invited discussant, Michael J. Overman, MD, Professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, Houston, said the findings of the study presented by Henriksen et al1 add to a convincing body of data showing that “the use of circulating tumor DNA [ctDNA] has the ability to robustly prognosticate patients after surgical resection for colorectal cancer.”

The tumor-informed approach in the study represents one of the detection approaches under investigation. It sequences a patient’s tumor to identify unique signatures of mutations; then, it custom designs and manufactures a personalized polymerase chain reaction assay, targeting the top 16 clonal mutations found in the tumor. According to the manufacturer, the turnaround time for the first time point is less than 4 weeks.

One thing is missing from the data, however, according to Dr. ­Overman: Can ctDNA serve as a predictive biomarker (ie, can adjuvant therapy change ctDNA status)? Four patients who tested positive for ctDNA did not experience recurrence, and all had adjuvant treatment, he pointed out. “Randomized prospective studies are needed to answer this question,” he proposed.

Michael J. Overman, MD

Michael J. Overman, MD

According to Dr. Overman, the study findings support the utility of ctDNA detection to identify molecular residual disease after surgical resection and to predict disease recurrence. If applied appropriately, he predicted, ctDNA monitoring could alter the paradigm for postoperative management of this disease. This not only relates to escalation and de-escalation of treatment, but to the use of this assay to replace current surveillance approaches, he suggested.

Moving Forward: More to Learn

However, it is critical for clinicians to understand how to use ctDNA to guide therapy, Dr. Overman added. “It must be recognized that the availability of a test is not the same as its actionability.”

Numerous phase II/III clinical trials have been launched to prospectively evaluate the power of ctDNA to direct disease management, using multiple approaches to ctDNA detection. These trials are leveraging ctDNA in several different ways, such as guiding adjuvant treatment intensification after surgery for patients with stage I and low-risk stage II colorectal cancer, guiding adjuvant treatment de-escalation after surgery for patients with high-risk stage II or III disease, and guiding intensification of radiologic surveillance in patients with high-risk stage II or III disease following surgery and adjuvant chemotherapy.

“I encourage all of us to support the enrollment of ongoing randomized clinical trials utilizing ctDNA to help optimize our use of adjuvant therapy for patients with colorectal cancer,” Dr. Overman said. 

DISCLOSURE: Dr. Overman has served as a consultant or advisor to Array BioPharma, Bristol Myers Squibb, Gritstone Oncology, Janssen, MedImmune, Novartis, Pfizer, Promega, Roche/Genentech, and Spectrum Pharmaceuticals and has received research funding from Bristol Myers Squibb, MedImmune, Merck, and Roche.

REFERENCE

1. Henriksen TV, Tarazona N, Reinert T, et al: Circulating tumor DNA analysis for assessment of recurrence risk, benefit of adjuvant therapy, and early relapse detection after treatment in colorectal cancer patients. 2021 Gastrointestinal Cancers Symposium. Abstract 11. Presented January 16, 2021.

 


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