Abstract
BACKGROUND: Plasma epidermal growth factor receptor (EGFR) mutation tests are widely used when non-small cell lung cancer (NSCLC) patients acquire resistance to EGFR inhibitors. We comprehensively evaluated the clinical utility of plasma EGFR test. METHODS: We screened NSCLC patients who had a plasma EGFR test upon acquiring resistance to first- or second-generation EGFR inhibitors. Plasma EGFR tests were performed with the EGFR mutation test. RESULTS: A total of 355 patients were tested for plasma EGFR mutations, and T790M was detected in 83 patients (23%). Of 79 patients who were tested multiple times, T790M was newly detected in 13 subsequent plasma tests. When initial plasma tests did not detect any EGFR mutation types, the detection rate of T790M in subsequent tests was very low (9%, 5/56), while detection rates of T790M in subsequent tests increased (35%, 8/23) in those individuals in whom sensitizing mutations had been detected in the initial plasma test (P=0.005). Paired plasma and tissue EGFR test results were available for 235 patients. Sensitivity and specificity of the plasma tests for T790M were 14% and 87%, respectively. Among 235 patients, 140 patients had tissue EGFR tests performed after T790M-negative plasma results were reported. The subsequent tissue test detected T790M in 61% (44/72) of these patients when any EGFR mutations were not detected in prior plasma tests, while the detection rate of T790M in subsequent tissue tests was 37% (25/68) when sensitizing mutations were detected in prior plasma tests (P=0.004). CONCLUSIONS: Because the sensitivity of plasma EGFR test for T790M is low, follow-up tissue or plasma tests are necessary. Presence or absence of a sensitizing mutation in the initial plasma tests can be used to determine which samples (tissue or plasma) should be submitted for further testing.