Trial Information

Detection of EGFR Mutations in the Blood of Patients With Non-Small Cell Lung Cancer: a Feasibility Study

The oral tyrosine kinase (TK) inhibitors of Epidermal Growth Factor Receptor (EGFR),
gefitinib and erlotinib, have produced dramatic responses, encouraging response rates and
possibly improved survival in a subset of NSCLC patients. Evidence suggests that somatic
EGFR mutations in the tumor are at present the single most reliable biological marker of
predicting response to EGFR TK inhibitors. In addition, these mutations may be an early
event in the pathogenesis of NSCLC in a subset of patients. Unfortunately, the technology of
EGFR mutations sequencing incurs high costs and requires sufficient tissue, which is often a
problem in NSCLC. We hypothesize that EGFR mutations can be detected in the blood and
propose a study to determine the feasibility of detecting EGFR mutations in the blood of
NSCLC patients. We will approach newly diagnosed NSCLC patients as well as patients who are
known to be responding to the oral TK inhibitors. We will perform EGFR mutations on the
tumors. For the blood, we will use new immuno-separation techniques to isolate tumor cells
and perform denaturing high performance liquid chromatography to detect EGFR mutations. If
we prove that it is feasible to detect the mutations in the blood, we will follow up with a
validation study. Many applications can result if our hypothesis holds true: 1) it will be
proof of principle that our technique can effectively isolate and detect somatic mutations
in circulating tumor cells, 2) it will be a simple way to overcome the problem of
insufficient tumor samples, 3) it can be used for early detection of lung cancer if EGFR
mutations proves to be important in pathogenesis in a subset of patients and 4) the
technology can be extended to detect new mutations in patients who become resistant to oral
TK inhibitors which can lead to new targeted therapies.