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Effective treatment of pulmonary adenocarcinoma harboring triple EGFR mutations of L858R, T790M, and cis-C797S by osimertinib, bevacizumab, and brigatinib combination therapy: a case report

Authors Zhao J, Zou M, Lv J, Han Y, Wang G, Wang G

Received 6 April 2018

Accepted for publication 29 June 2018

Published 6 September 2018 Volume 2018:11 Pages 5545—5550

DOI https://doi.org/10.2147/OTT.S170358

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 4

Editor who approved publication: Prof. Dr. Geoffrey Pietersz


Jing Zhao,1 Ming Zou,1 Jinyan Lv,2 Yingmin Han,1 Guangzhi Wang,3 Gang Wang2

1Department of Pharmacy, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 2Department of Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian, People’s Republic of China; 3Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, People’s Republic of China

Abstract: Osimertinib is commonly used in pulmonary adenocarcinoma patients who are resistant to first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and carry the T790M mutation. However, the use of osimertinib may result in the development of further resistance, most commonly via the cis-C797S mutation. Herein, we report a case of a lung cancer patient harboring triple EGFR mutations of L858R, T790M, and cis-C797S who was treated with a combination of osimertinib, bevacizumab, and brigatinib. The above 3 mutations were detected by circulating tumor DNA analysis after osimertinib treatment. Subsequently, the patient received combination therapy of osimertinib and bevacizumab; the partial relief obtained was negated by later disease progression. The regimen was then changed to osimertinib, bevacizumab, and brigatinib combination therapy. Partial remission was observed, and a significant reduction in EGFR mutations was detected. This case represents the first evidence that 1) bevacizumab combined with osimertinib can significantly relieve tumor growth and respiratory symptoms in non-small-cell lung cancer patients with osimertinib resistance and 2) the clinical use of osimertinib, bevacizumab, and brigatinib is effective as combination therapy for pulmonary adenocarcinoma in the presence of triple EGFR mutations of L858R, T790M, and cis-C797S. These combination therapies may provide potential novel treatment options for pulmonary adenocarcinoma patients.

Keywords: pulmonary adenocarcinoma, EGFR-T790M, EGFR cis-C797S, drug resistance mechanisms

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