Rebiopsy of non-small cell lung cancer patients with acquired resistance to EGFR-TKI: Comparison between T790M mutation-positive and -negative populations.

7528 Background: The secondary epidermal growth factor receptor (EGFR) mutation T790M accounts for approximately half of acquired resistances to EGFR-tyrosine kinase inhibitors (TKI). A recent report has demonstrated the presence of T790M predicts a favorable prognosis and indolent progression, compared to the absence of T790M after TKI failure. However, rebiopsy to confirm T790M status can be challenging due to limited tissue availability and procedural feasibility, and little is known regarding the differences among patients with or without T790M. Methods: We investigated 73 patients harboring EGFR sensitive mutations who had undergone rebiopsy to confirm the emergence of T790M after TKI failure. The peptide nucleic acid-locked nucleic acid PCR clamp method was used in EGFR mutational analyses. Patient characteristics (age, gender, smoking history, performance status, EGFR mutation site, initial TKI, response to initial TKI, line of initial TKI, progression-free survival with initial TKI, and biopsy site) and postprogression survivals (PPS) after initial TKI failure, were retrospectively compared in patients with and without T790M. Results: We identified T790M in 2 (10%) of 21 central nervous system (CNS) (19 cerebrospinal fluid and 2 brain tissue) specimens, and in 20 (38%) of 52 other lesions (25 lung tissue, 24 pleural effusion, and 3 lymph node) (p = 0.0225). Other characteristics had no statistical association with the detection of T790M. Median PPS in patients with T790M was 34.0 months, and in those without T790M, 14.5 months (p = 0.0038). Although none of our patients received TKIs continuously after initial failure, 56 (77%) patients were re-administered TKIs. Regardless of T790M status, PPS in patients with TKI re-administration (23.4 months) was significantly longer than without re-administration (10.4 months) (p = 0.0085). Conclusions: The emergence of T790M in CNS is rare compared with other lesions. Patients with T790M after TKI failure have significantly better prognosis than those without T790M. The effectiveness of TKI re-administration or continuous administration beyond progression is suggested after initial TKI failure.