Association of EGFR Exon 19 Deletion and EGFR-TKI Treatment Duration with Frequency of T790M Mutation in EGFR-Mutant Lung Cancer Patients.
The most common event responsible for resistance to first- and second-generation (1st and 2nd) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is acquisition of T790M mutation. We examined whether T790M is related to clinicopathologic or prognostic factors in patients with relapse of EGFR mutant non-small cell lung cancer (NSCLC) after treatment with 1st or 2nd EGFR-TKIs. We retrospectively reviewed the T790M status and clinical characteristics of 73 patients with advanced or recurrent NSCLC who had been treated with EGFR-TKIs and undergone rebiopsy at Kurume University Hospital between March 2005 and December 2015. T790M mutation was more frequent in patients with EGFR exon 19 deletion mutation (63%, 26/41) than in those with L858R mutation (38%, 12/32) (p = 0.035). The median total duration of 1st or 2nd EGFR-TKI treatment was significantly longer in patients with T790M mutation than in those without (15.3 months vs 8.1 months, p < 0.001). Multivariate analysis revealed that the type of EGFR mutation and the total duration of EGFR-TKI treatment were significantly associated with T790M prevalence. Patients with EGFR exon 19 deletion mutation who receive long-term EGFR-TKI therapy show a high prevalence of T790M mutation. The present data are potentially important for clinical decision-making in NSCLC patients with EGFR mutation.
Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Norikazu
N
Matsuo
Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Koichi
K
Azuma
Department of Genome Biology, Kinki University Faculty of Medicine, Osakasayama, Osaka, Japan.
Kazuko
K
Sakai
Biostatistics Center, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Satoshi
S
Hattori
Department of Diagnostic Pathology, Kurume University Hospital, Kurume, Fukuoka, Japan.
Akihiko
A
Kawahara
Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Hidenobu
H
Ishii
Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Takaaki
T
Tokito
Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Takashi
T
Kinoshita
Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Kazuhiko
K
Yamada
Biostatistics Center, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Kazuto
K
Nishio
Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Tomoaki
T
Hoshino
D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D017384:Sequence Deletion
D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors