Liquid Biopsies Hold Promise of Diagnosing Response to Chemotherapy Interview with:

Karen L. Reckamp, M.D. Associate Professor City of Hope Comprehensive Cancer Center Duarte, CA 91010

Dr. Karen Reckamp

Karen L. Reckamp, M.D.
Associate Professor
City of Hope Comprehensive Cancer Center
Duarte, CA 91010 What is the background for this study? What are the main findings?
• Approximately 60% of patients with non-small cell lung cancer (NSCLC) receiving EGFR tyrosine kinase inhibitors (TKIs) will develop TKI resistance through the acquisition of the EGFR T790M mutation.
• A major challenge for assessing EGFR mutation status in advanced NSCLC is the availability of suitable biopsy tissue for molecular testing, specifically for determination of the emergence of T790M following progression on initial EGFR TKI therapy.
• The objective of this study was to demonstrate that a highly sensitive and quantitative next-generation sequencing analysis of EGFR mutations is feasible from urine and plasma, providing comparable clinical information while potentially mitigating the issues associated with tissue biopsies.
• This blinded, retrospective study was conducted on matched tissue, urine and plasma specimens collected from 63 patients with Stage IIIB-IV NSCLC enrolled in the TIGER-X trial of rociletinib, an investigational 3rd generation tyrosine kinase inhibitor (TKI), targeting T790M. What is the background for this study? What are the main findings?

Response: The main findings of this study include:

  •  This is the first successful demonstration of EGFR mutation detection in the urine of patients with metastatic NSCLC.
  •  In the cohort of patients who relapsed on first line EGFR TKI therapy, the sensitivity of urine EGFR mutation detection, with tumor tissue as reference, was 72% (34/47) for T790M, 67% (28/42) for Exon 19 deletions, and 75% (12/16) for L858R mutations (10-100 mL urine volumes).
  • Sensitivity of mutation detection increased with urine volume. A higher mutation detection sensitivity was achieved with urine samples at the recommended volume of 90-100 mL: 93% (13/14) for T790M, 71% (5/7) for L858R, and 83% (10/12) for exon 19 deletions (90-100 mL).
  • A comparable sensitivity of EGFR mutation detection was observed in plasma: 93% (38 of 41 specimens) for T790M, 100% (17 of 17) for L858R, and 87% (34 of 39) for exon 19 deletions
  •  Of 63 cases presumably positive for T790M mutation based on local laboratory testing, utilizing central laboratory tissue testing alone identified 73% of cases as positive for T790M.
  •  Utilizing the minimally invasive liquid biopsies together, urine and plasma testing identified 93% of cases as T790M-positive, suggesting that urine and plasma testing can serve as a noninvasive alternative to tissue biopsies.
  •  T790M levels in urine rapidly fell to a fraction of their pretreatment levels in patients treated with rociletinib, suggesting that longitudinal monitoring of mutation levels in urine cell-free DNA may reflect tumor response to therapy.
  • Overall, urine testing using mutation enrichment NGS method successfully identifies EGFR mutations in patients with metastatic NSCLC and has high concordance with tumor tissue and plasma, suggesting that EGFR mutation detection from urine or plasma should be considered as a viable alternatives for assessing EGFR mutation status. What should readers take away from your report?
• Circulating tumor DNA from NSCLC can be detected with high sensitivity through liquid biopsy using either urine or blood, offering patients and healthcare providers a noninvasive diagnostic method to identify the EGFR T790M resistance mutation and potentially help physicians monitor a patient’s response to targeted therapy.
• T790M plasma, tissue, and urine tests complement one another; each test identifies a similar number of patients, and each identifies unique cases.
• Urine is a truly noninvasive alternative to tissue biopsy, and blood is a minimally invasive alternative. Both liquid biopsy sample types integrate DNA from multiple sites, thus potentially addressing the challenges posed by tumor heterogeneity. What recommendations do you have for future research as a result of this study?


• Given the ease of sample collection, urine holds promise for the diagnostic detection of actionable mutations and for the serial monitoring of patients’ response to therapy.
• Additional studies in plasma have demonstrated that early changes in circulating tumor DNA (ctDNA) may predict response to targeted therapies and that emergence of resistance mutations can be identified before detection of clinical progression by radiographic scans.
• Results also demonstrate the scientific importance of ongoing urine-based liquid biopsy research and continuing to advance technology and research to validate and expand its clinical utility. Is there anything else you would like to add?
• Our goal is to provide patients and physicians with a noninvasive test that can monitor tumor dynamics in real-time without adding to the overall physical, emotional and economic burden of care.
• The hope is that we will have plasma and urine testing available for patients so that we can avoid invasive biopsies for most patients in the future. Thank you for your contribution to the community.


Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

A Highly Sensitive and Quantitative Test Platform for Detection of NSCLC EGFR Mutations in Urine and Plasma

Reckamp, Karen L. et al.
Journal of Thoracic Oncology , Volume 0 , Issue 0 ,

 Published online July 24 2016

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