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Lung Cancer. 2014 Jul;85(1):19-24. doi: 10.1016/j.lungcan.2014.03.016. Epub 2014 Mar 23.

Incidence of T790M mutation in (sequential) rebiopsies in EGFR-mutated NSCLC-patients.

Author information

1
Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: jl.kuiper@vumc.nl.
2
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
3
Department of Cardiothoracic Surgery, VU University Medical Center, Amsterdam, The Netherlands.
4
Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands.

Abstract

AIM:

Non-small cell lung cancer (NSCLC)-patients with an epidermal growth factor receptor (EGFR)-mutation have median progression-free survival (PFS) of 12 months on tyrosine kinase inhibitors (TKIs). Resistance is mediated by the EGFR T790M-mutation in the majority of patients. Longitudinal follow-up data are lacking. We retrospectively evaluated EGFR-mutated NSCLC-patients who were rebiopsied after TKI-treatment. A subgroup was sequentially rebiopsied along the course of the disease.

PATIENTS AND METHODS:

Advanced EGFR-mutated NSCLC-patients who had both a pre-TKI biopsy and post-TKI biopsy available were included. Information on treatments and (re)biopsies was collected chronologically. Primary endpoint was the incidence of the T790M-mutation.

RESULTS:

Sixty-six patients fulfilled the inclusion criteria. In first post-TKI biopsies, T790M-mutation was detected in 34 patients (52%) of patients. Twenty-seven patients had subsequent post-TKI rebiopsies with mutation analysis available; in 10 patients (37%) the T790M-status in subsequent post-TKI rebiopsies was not consistent with the T790M-status of the first post-TKI biopsy. Progression free survival (PFS) on TKI-treatment was 12.0 months. Objective response rate on TKI-treatment was 81%. Patients developing T790M-mutation at post-TKI biopsy had longer median PFS compared to T790M-negative patients (14.2 versus 11.1 months respectively (P=0.034)) and longer overall survival (45.9 months versus 29.8 months respectively (P=0.213)). Transformation to SCLC was detected in 1 patient (2%).

CONCLUSION:

Incidence of T790M-mutation at first post-TKI biopsy in this cohort of EGFR-mutated NSCLC-patients was 52%. Detection of T790M-mutation was not consistent over time; some patients who were T790M-positive at first post-TKI biopsy became T790M-negative in later post-TKI rebiopsies and vice versa. T790M-positive patients showed longer PFS than T790M-negative patients. Whether the low incidence of transformation to SCLC is justifying post-TKI rebiopsy in EGFR-mutated NSCLC-patients with acquired TKI-resistance in regular clinical practice is debatable.

KEYWORDS:

EGFR mutation; NSCLC; Rebiopsy; T790M-mutation; TKI-resistance; Targeted therapy

PMID:
24768581
DOI:
10.1016/j.lungcan.2014.03.016
[Indexed for MEDLINE]
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