Response of a Novel KANK1::ALK Fusion to Alectinib in an Advanced Lung Adenocarcinoma: A Case Report

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Quanying Tang Department of Lung Cancer Surgery, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China

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Tong Li Department of Lung Cancer Surgery, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China

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Fan Ren Department of Lung Cancer Surgery, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China

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Xuanguang Li Department of Lung Cancer Surgery, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China

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WeiBo Cao Department of Lung Cancer Surgery, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China

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Haochuan Yu Department of Lung Cancer Surgery, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China

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Fuling Mao Department of Lung Cancer Surgery, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China

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Cancan Cao Department of Lung Cancer Surgery, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China

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Lingling Zu Department of Lung Cancer Surgery, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China

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Song Xu Department of Lung Cancer Surgery, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China

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More than 90 distinct fusion partners of ALK rearrangement have been identified. Different ALK fusions may exhibit different sensitivities to ALK tyrosine kinase inhibitors. The emergence of rare fusions poses significant challenges to targeted therapies. This study aimed to investigate the response of KANK1::ALK fusion to alectinib in an advanced lung adenocarcinoma. A novel KANK1::ALK fusion was identified by next-generation sequencing (NGS) and Ventana immunohistochemistry assessments. A 73-year-old woman who had never smoked was admitted with hemoptysis in May 2020. PET/CT revealed a nodule in the left upper lobe, with bilateral pulmonary and multiple lymph node metastases. The upper lobe nodule of the left lung was diagnosed as adenocarcinoma through bronchofiberscopy biopsy, resulting in a clinical diagnosis of stage IVA (cT1c,N3,M1a). Because the biopsy tissue was insufficient for NGS analysis, a blood-based genetic analysis was performed, revealing the presence of KRAS p.Q61R mutations. The patient received carboplatin and pemetrexed with pembrolizumab as first-line therapy, followed by maintenance therapy of pembrolizumab monotherapy. Although the tumor initially showed significant shrinkage, it unfortunately progressed further after 11 months. Subsequently, the patient was given carboplatin and pemetrexed with pembrolizumab again, but the tumor progression continued. An NGS using a rebiopsy of the left upper lobe tumor suggested a KANK1::ALK fusion. Alectinib was prescribed in January 2022, and a durable partial response was observed after 18 months. ALK rearrangements were observed in the broader spectrum of lung cancers. This study provided a potential treatment option for patients with KANK1::ALK fusions. Further studies are needed to understand the function of these fusions.

Submitted July 3, 2023; final revision received October 14, 2023; accepted for publication November 8, 2023. Published online February 15, 2024.

Disclosures: The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.

Funding: Research reported in this publication was supported by the National Natural Science Foundation of China (82172776; S. Xu), National Key Clinical Specialty Discipline Construction Program of China (TJYXZDXK-061B; S. Xu), Tianjin Postgraduate Research and Innovation Project (2022SKYZ122; Q. Tang), and Diversified Input Project of Tianjin National Science Foundation (21JCYBJC01770; S. Xu).

Supplementary material: Supplementary material associated with this article is available online at https://doi.org/10.6004/jnccn.2023.7107. The supplementary material has been supplied by the author(s) and appears in its originally submitted form. It has not been edited or vetted by JNCCN. All contents and opinions are solely those of the author. Any comments or questions related to the supplementary materials should be directed to the corresponding author.

Correspondence: Song Xu, MD, PhD, Department of Lung Cancer Surgery, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping, Tianjin 300052, P.R. China. Email: xusong198@hotmail.com

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