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Pretreatment Epidermal Growth Factor Receptor (EGFR) T790M Mutation Predicts Shorter EGFR Tyrosine Kinase Inhibitor Response Duration in Patients With Non–Small-Cell Lung Cancer
- Source :
- Journal of Clinical Oncology. 30:433-440
- Publication Year :
- 2012
- Publisher :
- American Society of Clinical Oncology (ASCO), 2012.
-
Abstract
- Purpose Patients with non–small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)–activating mutations have excellent response to EGFR tyrosine kinase inhibitors (TKIs), but T790M mutation accounts for most TKI drug resistance. This study used highly sensitive methods to detect T790M before and after TKI therapy and investigated the association of T790M and its mutation frequencies with clinical outcome. Patients and Methods Direct sequencing, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and next-generation sequencing (NGS) were used to assess T790M in the following two cohorts of patients with NSCLC: TKI-naive patients (n = 107) and TKI-treated patients (n = 85). Results were correlated with TKI treatment response and survival. Results MALDI-TOF MS was highly sensitive in detecting and quantifying the frequency of EGFR-activating mutations and T790M (detection limits, 0.4% to 2.2%). MALDI-TOF MS identified more T790M than direct sequencing in TKI-naive patients with NSCLC (27 of 107 patients, 25.2% v three of 107 patients, 2.8%, respectively; P < .001) and in TKI-treated patients (before TKI: 23 of 73 patients, 31.5% v two of 73 patients, 2.7%, respectively; P < .001; and after TKI: 10 of 12 patients, 83.3% v four of 12 patients, 33.3%, respectively; P = .0143). The EGFR mutations and their frequencies were confirmed by NGS. T790M was an independent predictor of decreased progression-free survival (PFS) in patients with NSCLC who received TKI treatment (P < .05, multivariate Cox regression). Conclusion T790M may not be a rare event before or after TKI therapy in patients with NSCLC with EGFR-activating mutations. The pretreatment T790M mutation was associated with shorter PFS with EGFR TKI therapy in patients with NSCLC.
- Subjects :
- Male
Oncology
Cancer Research
medicine.medical_specialty
Lung Neoplasms
Drug resistance
medicine.disease_cause
Bioinformatics
T790M
Carcinoma, Non-Small-Cell Lung
Internal medicine
medicine
Humans
In patient
Epidermal growth factor receptor
Lung cancer
Protein Kinase Inhibitors
Mutation
biology
business.industry
Proportional hazards model
medicine.disease
respiratory tract diseases
ErbB Receptors
Treatment Outcome
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
biology.protein
Female
Response Duration
business
Subjects
Details
- ISSN :
- 15277755 and 0732183X
- Volume :
- 30
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Oncology
- Accession number :
- edsair.doi.dedup.....4f8bcaba11a38812083479eb9a068fae
- Full Text :
- https://doi.org/10.1200/jco.2011.38.3224