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ALK rearrangements as mechanisms of acquired resistance to osimertinib in EGFR mutant non‐small cell lung cancer
Author(s) -
Hou Helei,
Sun Dantong,
Zhang Chuantao,
Liu Dong,
Zhang Xiaochun
Publication year - 2021
Publication title -
thoracic cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.823
H-Index - 28
eISSN - 1759-7714
pISSN - 1759-7706
DOI - 10.1111/1759-7714.13817
Subject(s) - osimertinib , crizotinib , medicine , lung cancer , gefitinib , bevacizumab , cancer research , adenocarcinoma , oncology , chemotherapy , epidermal growth factor receptor , cancer , malignant pleural effusion , ros1
Non‐small cell lung cancer (NSCLC) patients harboring EGFR sensitive mutations may benefit from treatment with EGFR TKIs. Osimertinib, which is an irreversible third‐generation EGFR TKI, has demonstrated a convincing efficacy, irrespective of whether it is used in first‐ or second‐line treatment. The acquired resistance mechanisms to osimertinib are highly complicated, and a variety of potential molecular mechanisms have been discovered, including C797S. Here, we determined that ALK rearrangement might be an underlying mechanism contributing to acquired resistance to osimertinib. In our report, a 60‐year‐old female patient with lung adenocarcinoma with an EGFR mutation was administered multiple treatments, including first‐line gefitinib and second‐line osimertinib. According to the next‐generation sequencing (NGS) assay after osimertinib failure, the emergence of an ALK rearrangement was considered to be a potentially acquired resistance mechanism to osimertinib. The combination of osimertinib and crizotinib then maintained a six‐month stable disease. VEGFA amplification was identified after osimertinib plus crizotinib treatment, and chemotherapy plus bevacizumab achieved a continuous stable disease over 21 months. In this study, we also summarized previously reported cases and concluded that ALK rearrangement is a rare but critical resistance mechanism to osimertinib. After failure of combined treatment with osimertinib plus crizotinib, comprehensive molecular profiling should be performed, and chemotherapy plus bevacizumab might be an optimal treatment especially for patients harboring VEGFA amplification.

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