A Single Institute Retrospective Analysis of the Testing for the EGFR-TKI Resistance Mutation T790M in Non-small Cell Lung Carcinoma Patients

Osimertinib is recommended by the Japanese Lung Cancer Society to be used for patients with T790M EGFR mutation with progressive disease after treatment with lst-line EGFR-TKIs for stage IV EGFR mutant non-small cell lung carcinoma (NSCLC). However, 2nd biopsy to confirm T790M status can be challenging because of different tumor locations and biopsy procedures. We retrospectively investigated the characteristics of 21 NSCLC patients who had undergone 2nd biopsy after the lst-line EGFR-TKI treatment. Tissue biopsy and liquid biopsy were performed for 18 and 12 patients, respectively. T790M mutation was positive in 46% of patients with tissue biopsy and in 17% of those with liquid biopsy. We detected carcinoma at the frequency of 59% by all kinds of tissue biopsies. However, there was a discrepancy in the sensitivity for carcinoma among biopsy procedures. In bronchoscopy, the sensitivity was as low as 31%, while the sensitivity was 83% in CT guided biopsy and 100% in cell blocks using pleural or ascitic fluid. Therefore, an appropriate biopsy procedure is essential. T790M mutation rate was lower in liquid biopsy because it was performed only in patients with negative tissue biopsy. Furthermore, the low sensitivity for mutation rate (50%) indicates small amount of cell-free tumor DNA. The sensitivity for mutation rate tended to be higher in cases with newly developed extra-thoracic metastases than in cases without these lesions, which suggests that the time of liquid biopsy is also an important factor.