Epidermal growth factor receptor (EGFR) mutations found in the circulating free tumor DNA (ctDNA) from the plasma of advanced non-small cell lung cancer (NSCLC) patients correlates well with the EGFR mutations from patient-matched tumor tissue DNA.
EGFR tyrosine kinase inhibitor (TKI) therapy is approved for EGFR activating mutation positive patients with advanced NSCLC, but the standard for determining mutation status is with DNA derived directly from tumor tissue, which can be limited or not available. A more abundant and less invasive source of tumor DNA may be cell free tumor DNA found circulating in the blood.
International researchers prospectively analyzed and compared tumor and matched plasma DNA for EGFR mutations from 1060 patients that were screened as part of a phase IV, open-label, single-arm, first-line gefitinib in EGFR mutation positive Caucasian patients. Also, when two plasma samples from the same patient were available the mutation status of each was compared.
The September issue of the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer (IASLC), reports that the mutation status concordance between tumor and matched plasma for 652 patients that had results for both was 94% (95% CI 92-96) with a sensitivity of 66% (CI 56-75) and specificity of 100% (CI 99-100).
The reproducibility between two plasma specimens from the same patient was also high with a mutation concordance of 97% (CI 94-99) for 224 matched specimens. Post-hoc analysis of the efficacy of first-line gefitinib revealed there was similar progression-free survival (PFS) for those with EGFR mutation positive tissue (9.7 months [CI 8.5-11.0]) versus both mutation positive tissue and plasma (10.2 months [CI 8.5-12.5]).
The authors acknowledge that "tumor tissue should be considered the preferred sample type when available, however, our encouraging results suggest that a single plasma-derived ctDNA sample may be considered appropriate for assessment of EGFR mutation status when tumor tissue is unavailable or exhausted".
"As there are no published guidelines for the use of ctDNA for EGFR mutation analysis in the absence of tumor tissue, these results may help address this current unmet need." Dr. Douillard, lead author of the study, says his next steps are to "look for resistance mutations, like T790M, during treatment to better understand mechanisms of resistance and anticipate later line treatment at progression".
For future research he also suggests "searching for other resistance mutations along the EGFR pathway, as well as other related pathways, and improving the sensitivity by using more powerful testing methods, like next generation sequencers".
First author Dr. Jean-Yves Douillard and co-author Dr. Gyula Ostoros are both members of IASLC.
About the IASLC
The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated to the study of lung cancer. Founded in 1974, the association's membership includes more than 4,000 lung cancer specialists in 80 countries. To learn more about IASLC please visit http://www.iaslc.org
Rob Mansheim | Eurek Alert!
Identifying drug targets for leukaemia
02.05.2016 | The Hong Kong Polytechnic University
A cell senses its own curves: New research from the MBL Whitman Center
29.04.2016 | Marine Biological Laboratory
If a person pushes a broken-down car alone, there is a certain effect. If another person helps, the result is the sum of their efforts. If two micro-particles are pushing another microparticle, however, the resulting effect may not necessarily be the sum their efforts. A recent study published in Nature Communications, measured this odd effect that scientists call “many body.”
In the microscopic world, where the modern miniaturized machines at the new frontiers of technology operate, as long as we are in the presence of two...
Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.
Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...
Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.
In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...
Honeycomb structures as the basic building block for industrial applications presented using holo pyramid
Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...
Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences (CAS). This work is about avoiding costly and unstable fullerenes.
Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences...
27.04.2016 | Event News
15.04.2016 | Event News
12.04.2016 | Event News
02.05.2016 | Life Sciences
02.05.2016 | Materials Sciences
02.05.2016 | Physics and Astronomy