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Epidermal growth factor receptor exon 20 mutation in lung cancer: types, incidence, clinical features and impact on treatment

Authors Noronha V, Choughule A, Patil VM, Joshi A, Kumar R, Susan Joy Philip D, Banavali S, Dutt A, Prabhash K

Received 25 January 2017

Accepted for publication 29 March 2017

Published 9 June 2017 Volume 2017:10 Pages 2903—2908

DOI https://doi.org/10.2147/OTT.S133245

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 3

Editor who approved publication: Dr XuYu Yang

Vanita Noronha,1,* Anuradha Choughule,2,* Vijay M Patil,1,* Amit Joshi,1 Rajiv Kumar,3 Deepa Susan Joy Philip,1 Shripad Banavali,2 Amit Dutt,4 Kumar Prabhash2

1Department of Medical Oncology, 2Department of Medical Oncology-Molecular Laboratory, 3Department of Pathology, Tata Memorial Hospital, 4Dutt Lab, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Mumbai, India

*These authors contributed equally to this work

Background: There are limited data available on the treatment and outcome of epidermal growth factor receptor (EGFR) exon 20-mutated lung cancer patients. Hence, we planned an analysis of the demographic details, clinical profile and survival of lung cancer patients with exon 20 mutations. We compared our results to patients with EGFR tyrosine kinase inhibitor (TKI)-sensitizing activating and EGFR/anaplastic lymphoma kinase (ALK)-negative mutations.
Methods: This was a retrospective analysis of lung cancer patients who were treated at our center between January 2010 and August 2014. We reviewed the results of EGFR mutation testing by real-time polymerase chain reaction and Sanger sequencing. We also reviewed the data relating to baseline demographics, clinical profile, patient treatment and outcome measures in terms of response and overall survival (OS).
Results: A total of 580 patients fulfilled the selection criteria. In all, 227 (39.1%) patients had EGFR TKI-sensitizing activating mutations, 20 (3.4%) patients had exon 20 insertion mutations and 333 patients were EGFR/ALK mutation negative (57.5%). The median OS was 5 months (95% confidence interval [CI] 0.17–9.8 months) in exon 20 insertion mutations, 16.1 months (95% CI 12.8–19.5 months) in EGFR TKI-sensitizing activating mutations and 10 months (95% CI 7.9–12.1 months) in EGFR/ALK mutation-negative patients. The median OS was significantly better for the EGFR TKI-sensitizing activating mutation group (P=0.000, log-rank test) and for the EGFR/ALK-negative group (P=0.037, log-rank test) compared to the exon 20-mutated group.
Conclusion: Exon 20 mutation results in a poorer OS prognosis compared to EGFR- and ALK-negative patients and patients harboring EGFR TKI-sensitizing activating mutations. The incidence of de novo exon 20 insertions was 3.4%. Different types of exon mutations seem to have different outcomes.

Keywords: exon 20, lung cancer, EGFR mutation, TKI resistance, insertions
 

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