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


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%).


CONCLUSIONS
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.
Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: jl.kuiper@vumc.nl.
J L
JL
Kuiper
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
D A M
DA
Heideman
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
E
E
Thunnissen
Department of Cardiothoracic Surgery, VU University Medical Center, Amsterdam, The Netherlands.
M A
MA
Paul
Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands.
A W
AW
van Wijk
Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands.
P E
PE
Postmus
Department of Pulmonary Diseases, VU University Medical Center, Amsterdam, The Netherlands.
E F
EF
Smit
D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000473:pathology; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D020125:Mutation, Missense; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012189:Retrospective Studies
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
EGFR mutation; NSCLC; Rebiopsy; T790M-mutation; TKI-resistance; Targeted therapy