A Case of Lung Adenocarcinoma Response to Alectinib Harboring a Rare EML4-ALK Variant, Exon 6 of EML4 Fused to Exon 18 of ALK

Authors: Lirong Liu MM1,2, Fangfang Hou MM1,2,3, Yufeng Liu MM3, Wenzhu Li MM1,2, and Haibo Zhang MD1,2,4,5
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  • 1 Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine;
  • | 2 Department of Oncology, Guangdong Provincial Hospital of Traditional Chinese Medicine;
  • | 3 The Second Clinical Medical College of Guangzhou University of Chinese Medicine;
  • | 4 Guangdong-Hong Kong-Macau Joint Laboratory on Chinese Medicine and Immune Disease Research; and
  • | 5 Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong, China.

More than 20 types of ALK fusion variant subtypes have been identified, including different fusion partner genes or EML4-ALK fusions with different breakpoints. However, different ALK fusions show different sensitivities to ALK-tyrosine kinase inhibitors (ALK-TKIs) and the emergence of rare fusions brings great challenges to the target therapy in clinic. We report a rare EML4-ALK (E6;A18) fusion in a patient with lung adenocarcinoma that responded well to alectinib. This is the second case of this rare variant reported but the first report of response to an ALK-TKI. This evidence is the first to show that alectinib may be effective for this rare fusion type of non–small cell lung cancer, and these findings have important implications for drug selection in patients with this subtype. Further studies are needed to understand the function of this variant.

Submitted February 23, 2021; final revision received June 17, 2021; accepted for publication June 21, 2021. Published online November 11, 2021.

Disclosures: The authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: This work was supported by funding from Science and Technology Planning Project of Guangdong Province (No. 2020B1212030006).

Correspondence: Haibo Zhang, MD, Department of Oncology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou 510120, China. Email: haibozh@gzucm.edu.cn
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