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South Asian J Cancer
2018 Jan 01;71:61-64. doi: 10.4103/sajc.sajc_215_17.
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Clinical outcome study of crizotinib in immunohistochemistry-proven echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene among Indian patients with adenocarcinoma lung.
Batra U
,
Aggarwal M
,
Jain P
,
Goyal P
,
Yadav A
,
Maheshwari U
,
Mehta A
.
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AIMS: The anaplastic lymphoma kinase (ALK) Break Apart FISH Probe Kit and Ventana anti-ALK (D5F3) CDx immunohistochemistry (IHC) assay are the Food and Drug Administration-approved companion diagnostic for targeted therapy with the ALK inhibitor crizotinib in lung cancers. The aim of this study was to assess the efficacy and safety of twice daily crizotinib tablet (250 mg) in IHC-proven echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene among Indian patients with adenocarcinoma lung in the routine clinical practice.
SUBJECTS AND METHODS: Patients with nonsmall cell lung cancer (NSCLC), adenocarcinoma histology, whose tumors were found to be positive for EML4-ALK fusion gene using IHC, were considered for this study. IHC analysis was performed using a Ventana automated immunostainer (Benchmark XT). Detection was performed using Optiview DAB detection and amplification kit.
RESULTS: A total of 25 NSCLC adenocarcinoma patients were included in the study. There were 14 (56%) women and 10 (44%) men with a median age of 53 years. All patients had Stage IV disease at the time of initiation of crizotinib therapy. One patient achieved complete response and 20 achieved response rate (PR) for an overall PR of 84%. The median progression-free survival (PFS) was 11.8 months and median overall survival (OS) was 20.6 months. Two (8%) patients experienced severe hepatotoxicity requiring permanent discontinuation of crizotinib therapy.
CONCLUSIONS: A very high PR, PFS, and OS achieved in our study population indicates that IHC can accurately identify EML4 ALK fusion gene mutations in lung adenocarcinoma patients who are responsive to ALK inhibitors such as crizotinib. IHC should be considered as a cost-effective alternative to FISH, especially in low-resource countries.
Ali,
Comprehensive Genomic Profiling Identifies a Subset of Crizotinib-Responsive ALK-Rearranged Non-Small Cell Lung Cancer Not Detected by Fluorescence In Situ Hybridization.
2016, Pubmed
Ali,
Comprehensive Genomic Profiling Identifies a Subset of Crizotinib-Responsive ALK-Rearranged Non-Small Cell Lung Cancer Not Detected by Fluorescence In Situ Hybridization.
2016,
Pubmed
Chougule,
Frequency of EGFR mutations in 907 lung adenocarcioma patients of Indian ethnicity.
2013,
Pubmed
Cortes-Funes,
Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small-cell lung cancer patients.
2005,
Pubmed
Desai,
A year of anaplastic large cell kinase testing for lung carcinoma: pathological and technical perspectives.
2013,
Pubmed
,
Echinobase
Doval,
Epidermal growth factor receptor mutation in lung adenocarcinoma in India: A single center study.
2013,
Pubmed
Doval,
Clinical and epidemiological study of EGFR mutations and EML4-ALK fusion genes among Indian patients with adenocarcinoma of the lung.
2015,
Pubmed
,
Echinobase
Huang,
Impact of smoking status and pathologic type on epidermal growth factor receptor mutations in lung cancer.
2011,
Pubmed
Jemal,
Cancer statistics, 2008.
2008,
Pubmed
Kwak,
Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer.
2010,
Pubmed
Lantuejoul,
French multicentric validation of ALK rearrangement diagnostic in 547 lung adenocarcinomas.
2015,
Pubmed
Lynch,
Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib.
2004,
Pubmed
Ma,
Responses to crizotinib in patients with ALK-positive lung adenocarcinoma who tested immunohistochemistry (IHC)-positive and fluorescence in situ hybridization (FISH)-negative.
2016,
Pubmed
Marchetti,
ALK Protein Analysis by IHC Staining after Recent Regulatory Changes: A Comparison of Two Widely Used Approaches, Revision of the Literature, and a New Testing Algorithm.
2016,
Pubmed
McLeer-Florin,
Dual IHC and FISH testing for ALK gene rearrangement in lung adenocarcinomas in a routine practice: a French study.
2012,
Pubmed
Okamoto,
The emerging role of epidermal growth factor receptor (EGFR) inhibitors in first-line treatment for patients with advanced non-small cell lung cancer positive for EGFR mutations.
2010,
Pubmed
Paik,
Screening of anaplastic lymphoma kinase rearrangement by immunohistochemistry in non-small cell lung cancer: correlation with fluorescence in situ hybridization.
2011,
Pubmed
Pekar-Zlotin,
Fluorescence in situ hybridization, immunohistochemistry, and next-generation sequencing for detection of EML4-ALK rearrangement in lung cancer.
2015,
Pubmed
Sahoo,
Screening for EGFR mutations in lung cancer, a report from India.
2011,
Pubmed
Sequist,
Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice.
2011,
Pubmed
Shaw,
Crizotinib versus chemotherapy in advanced ALK-positive lung cancer.
2013,
Pubmed
Shaw,
ALK in lung cancer: past, present, and future.
2013,
Pubmed
Soda,
Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
2007,
Pubmed
,
Echinobase
Thunnissen,
EML4-ALK testing in non-small cell carcinomas of the lung: a review with recommendations.
2012,
Pubmed
Tsao,
The future of NSCLC: molecular profiles guiding treatment decisions.
2011,
Pubmed
Usui,
The Frequency of Epidermal Growth Factor Receptor Mutation of Nonsmall Cell Lung Cancer according to the Underlying Pulmonary Diseases.
2011,
Pubmed
Wallander,
Comparison of reverse transcription-polymerase chain reaction, immunohistochemistry, and fluorescence in situ hybridization methodologies for detection of echinoderm microtubule-associated proteinlike 4-anaplastic lymphoma kinase fusion-positive non-small cell lung carcinoma: implications for optimal clinical testing.
2012,
Pubmed
,
Echinobase
Wang,
Crizotinib Versus Chemotherapy on ALK-positive NSCLC: A Systematic Review of Efficacy and Safety.
2019,
Pubmed
Wong,
The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS.
2009,
Pubmed
,
Echinobase
Wu,
Frequent epidermal growth factor receptor gene mutations in malignant pleural effusion of lung adenocarcinoma.
2008,
Pubmed
Ying,
Diagnostic value of a novel fully automated immunochemistry assay for detection of ALK rearrangement in primary lung adenocarcinoma.
2013,
Pubmed
Zhang,
Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression.
2010,
Pubmed
von Laffert,
Multicenter immunohistochemical ALK-testing of non-small-cell lung cancer shows high concordance after harmonization of techniques and interpretation criteria.
2014,
Pubmed
