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Predictors of Acquired T790M Mutation in Patients Failing First- or Second-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors

Authors Chai CS, Liam CK, Poh ME, Ong DBL, Pang YK, Cheah PL, Ho GF, Alip A

Received 24 March 2020

Accepted for publication 19 June 2020

Published 6 July 2020 Volume 2020:12 Pages 5439—5450

DOI https://doi.org/10.2147/CMAR.S253760

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Yong Teng


Chee-Shee Chai,1 Chong-Kin Liam,2 Mau-Ern Poh,2 Diana Bee-Lan Ong,3 Yong-Kek Pang,2 Phaik-Leng Cheah,3 Gwo-Fuang Ho,4 Adlinda Alip4

1Department of Medicine, Faculty of Medicine and Health Science, University Malaysia Sarawak, Kota Samarahan, Sarawak, Malaysia; 2Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 4Department of Clinical Oncology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

Correspondence: Mau-Ern Poh
Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia
Tel +60 3 7949 4422
Fax +60 3 7955 2253
Email ernestpoh@gmail.com

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.

Keywords: non-small cell lung cancer, epidermal growth factor receptor, acquired T790M mutation, independent predictor, tyrosine kinase inhibitor

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