REBIOPSY OF NON-SMALL-CELL LUNG CANCER PATIENTS WITH ACQUIRED RESISTANCE TO EGFR-TKI: COMPARISON BETWEEN T790M MUTATION-POSITIVE AND -NEGATIVE POPULATIONS

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Abstract

Background

The secondary EGFR mutation (MT) T790M accounts for approximately half of acquired resistances to EGFR-TKI. A recent report has demonstrated that the presence of T790M predicts a favorable prognosis and indolent progression, compared with the absence of T790M after TKI failure. However, rebiopsy to confirm the T790M status can be challenging due to limited tissue availability and procedural feasibility, and little is known about the differences among patients with or without T790M.

Methods

We investigated 73 patients harboring EGFR MTs who had undergone rebiopsy to confirm the emergence of T790M after TKI failure. The PNA-LNA PCR clamp method was used in EGFR MT analyses. Pt characteristics (age, gender, smoking history, performance status, EGFR MT site, initial TKI, response to initial TKI, line of initial TKI, PFS 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.

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