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Primary Resistance to Brigatinib in a Patient with Lung Adenocarcinoma Harboring ALK G1202R Mutation and LIPI-NTRK1 Rearrangement

Authors Xiao Z, Huang X, Xie B, Xie W, Huang M, Lin L

Received 13 February 2020

Accepted for publication 6 May 2020

Published 22 May 2020 Volume 2020:13 Pages 4591—4595


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Leo Jen-Liang Su

Zhiwei Xiao,1,* Xuewu Huang,1,* Biyuan Xie,2 Wenzhuan Xie,3 Mengli Huang,3 Lizhu Lin1

1Oncology Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, People’s Republic of China; 2Oncology Department, The Second Traditional Chinese Medicine Hospital of Guangdong Province, Guangzhou 510405, Guangdong, People’s Republic of China; 3The Medical Department, 3D Medicines Inc, Shanghai 201114, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Lizhu Lin Email

Purpose: Anaplastic lymphoma kinase (ALK) inhibitors have transformed the management of non-small-cell lung cancer (NSCLC) patients with ALK gene rearrangement. This paper reports a new resistance mechanism to a second-generation ALK inhibitor, brigatinib.
Case Report: A 43-year-old woman who had no history of smoking was diagnosed with stage IVa (T2bN2M1b) lung adenocarcinoma. After the first-line chemotherapy failed, the patient received crizotinib due to the presence of EML4-ALK fusion by next-generation sequencing (NGS). The patient had disease progression after 8 months on crizotinib, and a second NGS identified the ALK G1202R resistance mutation. Therefore, she was switched to brigatinib. After only 53 days of treatment with brigatinib, the patient developed a new 1.6× 1.2 cm lesion in the mediastinal lymph node. A third NGS testing revealed a new form of NTRK rearrangement (LIPI-NTRK1). The patient died 16 months after diagnosis.
Conclusion: This paper provides new insights into the primary resistance to brigatinib in NSCLC patients carrying ALK G1202R mutation. The new fusion form of NTRK rearrangement was detected, which may provide potential treatment options after brigatinib resistance.

Keywords: NTRK1, ALK, primary resistance, brigatinib, NSCLC

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