Lessons learned from routine, targeted assessment of liquid biopsies for EGFR T790M resistance mutation in patients with EGFR mutant lung cancers Journal Article


Authors: Mondaca, S.; Offin, M.; Borsu, L.; Myers, M.; Josyula, S.; Makhnin, A.; Shen, R.; Riely, G. J.; Rudin, C. M.; Ladanyi, M.; Yu, H. A.; Li, B. T.; Arcila, M. E.
Article Title: Lessons learned from routine, targeted assessment of liquid biopsies for EGFR T790M resistance mutation in patients with EGFR mutant lung cancers
Abstract: Background: Plasma cfDNA evaluation at acquired resistance to targeted therapies in lung cancer is routine, however, reports of extended clinical application and pitfalls in laboratory practice are still limited. In this study we describe our experience with cfDNA testing using EGFR T790M as a prototype. Methods: Patients with metastatic EGFR-mutant NSCLC patients who underwent plasma EGFR T790M testing at acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI) from January 2016 through August 2017 were identified. Molecular laboratory records were reviewed to assess performance of testing by digital PCR, concordance between plasma and tissue testing, turnaround time (TAT), plasma T790M variant allele frequency (VAF), and its correlations with metastatic sites and clinical outcomes. Results: 177 patients underwent T790M cfDNA testing during this period. Plasma T790M was positive in 32% of patients. The median TAT was shorter for plasma T790M compared to tissue PCR (9 vs. 15 days, p <.0001), and led to osimertinib use in 84% of positive patients. In 52 patients with plasma and tissue T790M evaluation, the concordance was 77%. Plasma T790M VAF did not correlate with time to osimertinib discontinuation (p =.4). Plasma T790M status correlated with a higher number of metastatic sites (4 vs. 3, p <.001) and bone metastases (p =.0002). Conclusion: Plasma EGFR T790M testing had shorter TAT compared to tissue testing, however, it was longer than anticipated. Test sensitivity is higher in patients with osseous metastases and with higher metastatic burden suggesting a more limited role for early detection. T790M VAF was not associated with clinical outcomes. © 2019, © 2019 Acta Oncologica Foundation.
Keywords: adult; controlled study; human tissue; aged; gene mutation; major clinical study; drug withdrawal; cancer patient; comparative study; disease association; epidermal growth factor receptor; gene frequency; retrospective study; electronic medical record; gene identification; genetic screening; turnaround time; non small cell lung cancer; medical history; clinical outcome; next generation sequencing; human; male; female; priority journal; article; osimertinib; liquid biopsy; chloroplast dna; digital polymerase chain reaction
Journal Title: Acta Oncologica
Volume: 58
Issue: 11
ISSN: 0284-186X
Publisher: Informa Healthcare  
Date Published: 2019-11-01
Start Page: 1634
End Page: 1639
Language: English
DOI: 10.1080/0284186x.2019.1645354
PUBMED: 31347936
PROVIDER: scopus
PMCID: PMC7480496
DOI/URL:
Notes: Article -- Source: Scopus
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MSK Authors
  1. Ronglai Shen
    204 Shen
  2. Helena Alexandra Yu
    281 Yu
  3. Marc Ladanyi
    1328 Ladanyi
  4. Gregory J Riely
    599 Riely
  5. Maria Eugenia Arcila
    657 Arcila
  6. Charles Rudin
    489 Rudin
  7. Bob Tingkan Li
    278 Li
  8. Michael David Offin
    170 Offin
  9. Mackenzie Myers
    15 Myers
  10. Alex Makhnin
    19 Makhnin