Brigatinib and lorlatinib: their effect on ALK inhibitors in NSCLC focusing on resistant mutations and central nervous system metastases

2020 ◽  
Vol 51 (1) ◽  
pp. 37-44
Author(s):  
Tomoyuki Naito ◽  
Hideaki Shiraishi ◽  
Yutaka Fujiwara
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lung Carcinoma ◽  
Anaplastic Lymphoma Kinase ◽  
Antitumour Activity ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Anaplastic Lymphoma

Abstract Major issues in anaplastic lymphoma kinase-positive non-small cell lung carcinoma are acquired resistance against anaplastic lymphoma kinase inhibitors and control of central nervous system metastasis. The development of these inhibitors has changed therapeutic strategy in patients with advanced anaplastic lymphoma kinase-positive non-small cell lung carcinoma. Brigatinib and lorlatinib were designed to penetrate the blood–brain barrier and to inhibit resistant mutations against anaplastic lymphoma kinase inhibitors. We review the clinical data supporting treatment of advanced anaplastic lymphoma kinase-positive non-small cell lung carcinoma with brigatinib and lorlatinib. Brigatinib has shown promising antitumour activity, including substantial activity against central nervous system metastases, in crizotinib-treated (ALTA trial) patients and crizotinib-naïve (ALTA-1L trial) patients with anaplastic lymphoma kinase-positive non-small cell lung carcinoma. In addition, brigatinib improved progression-free survival compared with crizotinib in anaplastic lymphoma kinase inhibitor-naïve patients with anaplastic lymphoma kinase-positive non-small cell lung carcinoma. Lorlatinib has demonstrated clinical antitumour activity against both intracranial and extracranial lesions in patients with anaplastic lymphoma kinase- or c-ros oncogene 1 (ROS1)-positive non-small cell lung carcinoma. Ongoing trials and further studies of these agents’ biological and clinical properties would provide insight into the optimal therapeutic strategy for administering them to achieve the best survival benefit.

scholarly journals Molecular Pathology of Lung Cancer Cytology Specimens: A Concise Review

2018 ◽  
Vol 142 (9) ◽  
pp. 1127-1133 ◽  
Author(s):  
Deepali Jain ◽  
Sinchita Roy-Chowdhuri
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Mutation Testing ◽  
Small Cell ◽  
Molecular Techniques ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Anaplastic Lymphoma ◽  
Google Search

Context.— There has been a paradigm shift in the understanding of molecular pathogenesis of lung cancer. A number of oncogenic drivers have been identified in non–small cell lung carcinoma, such as the epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) gene rearrangement. Because of the clinical presentation at an advanced stage of disease in non-small cell lung carcinoma patients, the use of minimally invasive techniques is preferred to obtain a tumor sample for diagnosis. These techniques include image-guided biopsies and fine-needle aspirations, and frequently the cytology specimen may be the only tissue sample available for the diagnosis and molecular testing for these patients. Objective.— To review the current literature and evaluate the role of cytology specimens in lung cancer mutation testing. We reviewed the types of specimens received in the laboratory, specimen processing, the effect of preanalytic factors on downstream molecular studies, and the commonly used molecular techniques for biomarker testing in lung cancer. Data Sources.— PubMed and Google search engines were used to review the published literature on the topic. Conclusions.— Mutation testing is feasible on a variety of cytologic specimen types and preparations. However, a thorough understanding of the cytology workflow for the processing of samples and appropriate background knowledge of the molecular tests are necessary for triaging, and optimum use of these specimens is necessary to guide patient management.

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