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Predictors of Acquired T790M Mutation in Patients Failing First- or Second-Generation Epidermal Growth Factor
Chee-Shee Chai1, Chong-Kin Liam2, Mau-Ern Poh2
1Department of Medicine, Faculty of Medicine and Health Science, University Malaysia Sarawak, Kota Samarahan, Sarawak, Malaysia.
Background:
This study aims to determine the predictors of acquired exon 20 T790M mutation in advanced non-small cell lung cancer (NSCLC) patients harbouring sensitizing epidermal growth factor receptor (EGFR) mutation following the failure of first- or second-generation EGFR-tyrosine kinase inhibitor (TKI).
Methods:
This is a retrospective observational study of NSCLC patients with sensitising EGFR mutation experiencing disease progression (PD) whilst on first- or second-generation EGFR-TKIs with subsequent investigations to detect acquired T790M mutation at the University of Malaya Medical Centre from 1st January 2015 to 31st December 2017.
Results:
A total of 87 patients were included. Upon PD, acquired T790M mutation was found in 55 (63.2%) patients and was significantly more common in patients who achieved partial response (PR) whilst on the EGFR-TKIs (p = 0.008) or had new lung metastasis upon PD (p = 0.048). It was less frequent in patients who developed new symptomatic brain lesions (p = 0.021). Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (p = 0.077). Multivariate analysis revealed PR whilst on EGFR-TKI treatment was an independent predictor of acquiring T790M mutation (p = 0.021), whereas development of new symptomatic brain lesions (p = 0.034) or new lymph node metastases (p = 0.038) upon PD was independently against acquiring T790M mutation. Patients with exon 19 deletion were more likely to acquire T790M mutation compared to those with exon 21 L858R point mutation (odds ratio: 2.3, 95% confidence interval: 0.84-6.25, p = 0.104).
Conclusion:
The best tumour response of PR to first- or second-generation EGFR-TKI treatment independently predicts acquired T790M mutation. Patients with exon 19 deletion are likely to acquire T790M mutation. This would prove useful for clinicians to prognosticate and plan subsequent treatments for patients with advanced NSCLC harbouring EGFR mutations.
Insights
Partial response to EGFR-TKI treatment predicts acquired T790M mutation in advanced NSCLC. Patients with exon 19 deletions are more likely to develop this mutation, aiding treatment planning.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Investigating acquired T790M mutations in advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations.
- Focus on patients who have progressed on first- or second-generation EGFR-TKIs.
Purpose of the Study:
- Identify predictors of acquired T790M mutation.
- Inform clinical decision-making for advanced NSCLC patients with EGFR mutations.
Main Methods:
- Retrospective observational study.
- Analysis of 87 NSCLC patients with sensitizing EGFR mutations.
- Data collected from January 2015 to December 2017 at University of Malaya Medical Centre.
Main Results:
- Acquired T790M mutation found in 63.2% of patients.
- Predictors include partial response to EGFR-TKI and new lung metastasis.
- Less frequent in patients with new symptomatic brain lesions.
- Exon 19 deletions more likely to acquire T790M than exon 21 L858R.
Conclusions:
- Partial response to EGFR-TKI is an independent predictor of acquired T790M mutation.
- Exon 19 deletion is associated with higher likelihood of T790M acquisition.
- Findings aid prognostication and treatment planning for advanced NSCLC.
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