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!
Killer sea snail a target for new drugs
07.07.2015 | University of Queensland
First images of dolphin brain circuitry hint at how they sense sound
07.07.2015 | Emory Health Sciences
When a duck paddles across a pond or a supersonic plane flies through the sky, it leaves a wake in its path. Wakes occur whenever something is traveling...
Researchers explore ultrafast control of magnetism across interfaces: A new study discovers how the sudden excitation of lattice vibrations in a crystal can trigger a change of the magnetic properties of an atomically-thin layer that lies on its surface.
A research team, led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter at CFEL in Hamburg, the University of Oxford, and the...
Wind turbines could be installed under some of the biggest bridges on the road network to produce electricity. So it is confirmed by calculations carried out by a European researchers team, that have taken a viaduct in the Canary Islands as a reference. This concept could be applied in heavily built-up territories or natural areas with new constructions limitations.
The Juncal Viaduct, in Gran Canaria, has served as a reference for Spanish and British researchers to verify that the wind blowing between the pillars on this...
New technique combines electron microscopy and synchrotron X-rays to track chemical reactions under real operating conditions
A new technique pioneered at the U.S. Department of Energy's Brookhaven National Laboratory reveals atomic-scale changes during catalytic reactions in real...
Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and a half billion years ago.
Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and...
25.06.2015 | Event News
16.06.2015 | Event News
11.06.2015 | Event News
07.07.2015 | Physics and Astronomy
07.07.2015 | Earth Sciences
07.07.2015 | Physics and Astronomy