MedicalResearch.com Interview with:
Erica L. Carpenter, MBA, PhD
Research Assistant Professor, Department of Medicine
Director, Circulating Tumor Material Laboratory
Division of Hematology/Oncology
Abramson Cancer Center
Perelman School of Medicine at the University of Pennsylvania
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The advent of precision medicine practices for cancer patients, including the use of drugs that target specific tumor mutations, has necessitated improved diagnostics with real-time molecular monitoring of patients’ tumor burden. While biopsy material, obtained surgically or through fine needle aspirate, can provide tissue for next generation sequencing (NGS) and mutation detection, this requires an invasive often painful procedure for the patient. In many cases, especially in more advanced disease when multiple metastases are present, such tissue cannot be obtained or can only be obtained from a single tumor site, thus limiting the sensitivity of tissue-based biopsy.
Here we report on a prospective cohort of 102 consecutively enrolled patients with advanced non-small lung cancer (NSCLC) for whom a non-invasive liquid biopsy was used for real-time detection of therapeutically targetable mutations. Tissue samples were only obtainable for 50 of the 102 patients, and these tissue biopsies were analyzed using a 47-gene Next Generation Sequencing (NGS) panel at Penn’s Center for Personalized Diagnostics. Concordance of results for the 50 patients who received both tests was close to 100% when the samples were obtained concurrently.
MedicalResearch.com: What should readers take away from your report?
Response: Liquid biopsies, such as NGS of circulating tumor DNA, provide clinically actionable data in real-time to assist with the management of NSCLC patients. This includes identification of patients who develop resistance to targeted therapies and may be candidates for second- or third-line inhibitors, but for whom a tissue biopsy is either not indicated or sufficient tissue or DNA for NGS was not obtainable. These non-invasive approaches for patient monitoring may reduce patient pain and suffering while providing powerful information to treating physicians to help determine the best course of treatment.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: Our study reports on a cohort of lung cancer patients with advanced disease who have already received one or more therapies. An important next step will be to evaluate the use of circulating tumor DNA as a complement to tissue testing at the diagnosis of lung cancer. In addition, this study only evaluated serial ctDNA testing for six patients, and larger studies will be necessary to accurately measure the clinical usefulness of obtaining multiple liquid biopsies over the course of a patient’s disease.
Finally, the use of checkpoint inhibitors and other forms of immune therapy have demonstrated efficacy in the treatment of lung and other cancer patients. Future research will need to be done to evaluate how ctDNA NGS can be used to predict which patients are candidates for immune therapies, and whether serial ctDNA testing can be effectively used to detect response and/or resistance to checkpoint inhibitors.
MedicalResearch.com: Is there anything else you would like to add?
Response: This pilot study to assess the feasibility of liquid biopsy monitoring of patients with advanced lung cancer represents the beginning of a paradigm shift in which tissue sequencing may no longer be considered the gold standard for molecular cancer monitoring. Such liquid biopsies will likely address an urgent unmet need for better, non-invasive tests as recently defined in the “Moonshot” Blue Ribbon Panel Report.
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Detection of therapeutically targetable driver and resistance mutations in lung cancer patients by next generation sequencing of cell-free circulating tumor DNA
Jeffrey C Thompson, Stephanie S Yee, Andrea B Troxel, Samantha L Savitch, Ryan Fan, David Balli, David B Lieberman, Jennifer D Morrissette, Tracey L Evans, Joshua Bauml, CHARU AGGARWAL, John A Kosteva, Evan Alley, Christine Ciunci, Roger B Cohen, Stephen Bagley, Susan Stonehouse-Lee, Victoria E Sherry, Elizabeth Gilbert, Corey Langer, Anil Vachani and Erica L Carpenter
DOI: 10.1158/1078-0432.CCR-16-1231 Published September 2016
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