Treatment benefit can be predicted through genotyping from blood plasma, according to several studies presented at the European Lung Cancer Conference (ELCC) 2016; however, plasma tests are unlikely to fully replace tissue biopsies.1
Mutations in the epidermal growth factor receptor (EGFR) indicate that patients with non-small cell lung cancer (NSCLC) are eligible for therapy that targets EGFR. While tissue biopsies are the gold standard, they are not obtainable from approximately 20% of patients with NSCLC. Instead, EGFR mutation status can potentially be analyzed through extracting circulating tumor DNA (ctDNA) from blood plasma.
The ASSESS trial, whose primary results were presented at ELCC 2016, examined how patient disease and demographic characteristics might affect detection of EGFR mutations in plasma. Sensitivity of EGFR mutation detection increased in plasma associated with increasing number and severity of metastases. Also, detection of EGFR mutations was significantly higher in patients younger than 65 years vs older patients. The companion IGNITE study independently confirmed these findings.
In addition, an analysis of the phase 1 AURA trial of osimertinib evaluated its effectiveness based on tumor or plasma results. Osimertinib is a third generation T790M targeting EGFR inhibitor.
Positive T790M biopsies correlated with high response rates and long progression-free survival (PFS) in the AURA trial, while those with T790M negative tumors had a low response rate and modest PFS. Patients with T790M positive plasma had high response rates and long PFS. However, those with T790M negative plasma had mixed outcomes.
“The first conclusion is that a noninvasive blood test appears to have the ability to find T790M-positive patients very effectively,” said Geoffrey Oxnard, MD, a thoracic cancer physician at the Dana-Farber Cancer Institute, in Boston, Massachusetts, and lead author of the study. “But the blood test only has a sensitivity of 70% or 80% so there are false negatives. In other words, if you have a negative result in the blood test it may be that the mutation was present but not detected.”
1. European Society for Medical Oncology. Plasma genotyping to predict treatment benefit in patients with NSCLC [news release]. EurekAlert! Web site. http://www.eurekalert.org/pub_releases/2016-04/esfm-pgt041216.php. Accessed May 2, 2016.