Plasma cfDNA Can Monitor Response To Metastatic Colon Cancer Treatment

Van K. Morris, M.D. Assistant Professor, GI Medical Oncology University of Texas – M.D. Anderson Cancer Center Houston, TX 77030

Dr. Morris

MedicalResearch.com Interview with:
Van K. Morris,  M.D.
Assistant Professor, GI Medical Oncology
University of Texas – M.D. Anderson Cancer Center
Houston, TX 77030 

Medical Research: What is the background for this study? What are the main findings?

Dr. Van K Morris: BRAF V600E mutations are associated with poor clinical outcomes for patients with metastatic colorectal cancer.  Patients were enrolled in a phase I clinical trial with the BRAF inhibitor vemurafenib, the anti-EGFR antibody cetuximab, and irinotecan.  Blood  samples were collected every two weeks with each dose, and plasma was analyzed for changes in the fraction of mutant BRAF V600E allele relative to wild-type BRAF allele with time.  Trends in circulating free DNA (cfDNA) changes were compared with radiographic changes by RECIST 1.1 criteria to examine this technique as a marker for response to therapy.

For patients who had a response radiographically, drastic reductions in the BRAF V600E allele fraction were observed even after two weeks of starting therapy, well before the first restaging scan.  Patients who did not have responses radiographically had less  dramatic changes relative to baseline in the BRAF V600E allele fraction.  This technique analyzing cfDNA from plasma was validated using two different approaches – digital droplet PCR and next-generation sequencing by Guardant Health.  Sequencing of cfDNA was also compared in pretreatment and post-progression samples, and novel mutations in MEK1 and GNAS were observed uniquely in post-progression samples.

Medical Research: What should clinicians and patients take away from your report?

Dr. Van K Morris: These findings demonstrate that analyzing plasma samples for dynamic changes over the course of a given treatment is feasible and may be a less invasive method than tissue biopsies to assess evolving tumor biology.  cfDNA can be used not only to assess a response to a particular therapy, but also at progression to inform potentially on targeted therapies based on the mutation profile at a specific point in time.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Van K Morris: These results need to be validated in larger cohorts of patients.  Potentially, the information gained from “liquid biopsies” may replace traditional, more invasive needle biopsies to understand the molecular drivers of a tumor.

Citation:

Abstract presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics

Circulating cell-free DNA as a marker for response and resistance to BRAF and EGFR inhibition in BRAF-mutated metastatic colorectal cancer
Van Morris, MD, MD Anderson Cancer Center, Houston, Texas

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Van K. Morris, M.D. (2015). Plasma cfDNA Can Monitor Response To Metastatic Colon Cancer Treatment 

Last Updated on November 10, 2015 by Marie Benz MD FAAD