Case Report
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. May 26, 2019; 7(10): 1221-1229
Published online May 26, 2019. doi: 10.12998/wjcc.v7.i10.1221
Significant benefits of osimertinib in treating acquired resistance to first-generation EGFR-TKIs in lung squamous cell cancer: A case report
Yan Zhang, Hui-Min Chen, Yong-Mei Liu, Feng Peng, Min Yu, Wei-Ya Wang, Heng Xu, Yong-Sheng Wang, You Lu
Yan Zhang, Hui-Min Chen, Yong-Mei Liu, Feng Peng, Min Yu, Yong-Sheng Wang, You Lu, Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Wei-Ya Wang, Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Heng Xu, Precision Medicine Center, State Key Laboratory of Biotherapy, Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Zhang Y and Chen HM contributed equally to this work; all authors contributed to the acquisition of data and writing and revision of this manuscript.
Supported by the National Natural Science Foundation of China, No. 81402561.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2013), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Yan Zhang, PhD, Doctor, Professor, Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu 610041, Sichuan Province, China. zhang.yan@gmx.com
Telephone: +86-28-85422571 Fax: +86-28-85422571
Received: January 2, 2019
Peer-review started: January 4, 2019
First decision: January 27, 2019
Revised: February 19, 2019
Accepted: March 16, 2019
Article in press: March 16, 2019
Published online: May 26, 2019
Processing time: 145 Days and 19.5 Hours
Abstract
BACKGROUND

Lung squamous cell cancer (LSCC) rarely harbors epidermal growth factor receptor (EGFR) mutations, even much rarer for acquired T790M mutation. Although clinical trials of AURA series illustrated that non-small cell lung cancer (NSCLC) with EGFR T790M mutation can benefit from osimertinib, only five LSCC patients were enrolled in total; moreover, the efficacy for LSCC was not shown in the results. Therefore, the response of LSCC to osimertinib is still unclear to date.

CASE SUMMARY

We report an LSCC case with T790M-related acquired resistance after treatments with first-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and benefited from osimertinib significantly. A 63-year-old Chinese man was diagnosed with stage IV (cT2N2M1b) LSCC harboring an EGFR exon 19-deletion mutation. Following disease progression after gefitinib and multi-line chemotherapy, re-biopsy was conducted. Molecular testing of EGFR by amplification refractory mutation system-polymerase chain reaction detected the exon 19-deletion without T790M mutation. Therefore, the patient was given erlotinib, but progression developed only 3 mo later. Then the frozen re-biopsy tissue was tested by next-generation sequencing (NGS), which detected an EGFR T790M mutation. However, he was very weak with symptoms of dysphagia and cachexia. Fortunately, osimertinib was started, leading to alleviation from the symptoms. Four months later, normal deglutition was restored and partial response was achieved. Finally, the patient achieved an overall survival time period of 29 mo.

CONCLUSION

Our findings highlight that EGFR T790M mutation may also be an important acquired drug resistance mechanism for LSCC and offer direct evidence of the efficacy of osimertinib in LSCC with T790M mutation. NGS and better preservation conditions may contribute to higher sensitivity of EGFR T790M detection.

Keywords: Lung squamous cell cancer; Lung cancer; Epidermal growth factor receptor mutation; T790M; Osimertinib; Tyrosine kinase inhibitor; Targeted therapy; Case report

Core tip: This is a case report of T790M-related acquired drug resistant lung squamous cell cancer (LSCC) patient with good response to osimertinib, which indicated that T790M is also an important mechanism for acquired resistance in LSCC. In this case, the secondary T790M mutation of epidermal growth factor receptor (EGFR) was detected by next-generation sequencing (NGS) for frozen tissue but not detected by amplification refractory mutation system-polymerase chain reaction for formalin-fixed and paraffin-embedded sample, which suggests that NGS and better preservation conditions may contribute to higher sensitivity of EGFR T790M detection.