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Using ctDNA to identify patients who could benefit from a switch in their therapeutic regimen.

The results of CCTG BR36 trial, recently published in the journal Nature Medicine, suggest that circulating tumor DNA (ctDNA) analyses could be used as an early marker of immunotherapy response and may help guide therapy.

“There is an unmet clinical need to implement real-time, minimally invasive molecular analyses to understand patients’ responses to cancer treatments and guide clinical decision-making,” says lead study author Valsamo Anagnostou, M.D., Ph.D., director of the thoracic oncology biorepository at Johns Hopkins, and co-director of the Lung Cancer Precision Medicine Center of Excellence.

Liquid biopsies (blood tests) can measure ctDNA which is cell-free DNA that is shed into the bloodstream by dying cancer cells. For advanced non-small cell lung cancer patients undergoing immunotherapy, it could identify those who could benefit from treatment with additional drugs.

“The potential for liquid biopsies in clinical practice for oncology is immense. Our goal is to ensure that we implement this technology in a rapid and effective way to help the care of our patients. This study provides critical information to aid in personalizing treatment strategies based on ctDNA responses to immunotherapy,” says Dr Cheryl Ho the Canadian study chair and a medical oncologist at Vancouver Cancer Centre.

The first stage of the BR36 trial found that by serial testing ctDNA, immunotherapy responses were detected early, within an average of eight weeks after treatment started. A ctDNA response (ctDNA no longer detected in the blood) reflected tumor shrinkage by imaging, however, there were notable exceptions that showed that ctDNA response may capture survival more accurately, especially for patients with stable disease on imaging.

“ctDNA has the potential to improve our ability to advise patients on the best treatment options for them. Our initial study indicates promising results, and we will move forward with a larger trial to clearly show whether ctDNA monitoring provides useful information based on treatment recommendations,” states, Dr Janet Dancey, director of the Canadian Cancer Trials Group.

Press Release by Johns Hopkins Research


About the trial

The trial is led by investigators at the Johns Hopkins Kimmel Cancer Center and its Bloomberg Kimmel Institute for Cancer Immunotherapy, BC Cancer and the Canadian Cancer trials Group (CCTG).

Study coauthors were Cheryl Ho, Canadian Study Chair, Vancouver Cancer Centre in British Columbia, Canada, and Benjamin Levy, Julie Brahmer, Archana Balan and Noushin Niknafs of Johns Hopkins. other authors were from the Ottawa Hospital in Canada; Juravinski Cancer Centre in Hamilton, Canada; Princess Margaret Cancer Centre in Toronto, Canada; Kingston Health Sciences Centre in Kingston, Canada; Canadian Cancer Trials Group in Kingston, Canada; Personal Genome Diagnostics (Labcorp) in Baltimore; and the Cancer Research Institute in New York, N.Y.

The trial was funded by the Cancer Research Institute, the Mark Foundation for Cancer Research and Personal Genome Diagnostics. The analyses were supported in part by the Canadian Cancer Society (grant 707213); the U.S. National Institutes of Health (grant CA121113) and the Commonwealth Foundation.

Dr Cheryl Ho
Dr Cheryl Ho the Canadian study chair and a medical oncologist at Vancouver Cancer Centre
Dr Anagnostou BR36
Study lead Dr Anagnostou, director, Johns Hopkins of the thoracic oncology biorepository
Janet Dancey director the canadian cancer trials group
Dr Janet Dancey, director of the Canadian Cancer Trials Group