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CC BY-NC-ND 4.0 · South Asian J Cancer 2018; 07(01): 61-64
DOI: 10.4103/sajc.sajc_215_17
ORIGINAL ARTICLE: Lung Cancer

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

Ullas Batra
Rajiv Gandhi Cancer Institute and Research Center, New Delhi
,
Mohit Aggarwal
Rajiv Gandhi Cancer Institute and Research Center, New Delhi
,
Parveen Jain
Rajiv Gandhi Cancer Institute and Research Center, New Delhi
,
Pankaj Goyal
Rajiv Gandhi Cancer Institute and Research Center, New Delhi
,
Abhishek Yadav
Rajiv Gandhi Cancer Institute and Research Center, New Delhi
,
Udip Maheshwari
Rajiv Gandhi Cancer Institute and Research Center, New Delhi
,
Anurag Mehta
Rajiv Gandhi Cancer Institute and Research Center, New Delhi
› Author Affiliations Financial support and sponsorship Nil.
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Abstract

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.

Key words

Echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase - epidermal growth factor receptor - nonsmall cell lung cancer - small cell lung cancer


Publication History

Article published online:
22 December 2020

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  • References

  • 1 Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin 2008;58:71-96.
  • 2 Okamoto I, Mitsudomi T, Nakagawa K, Fukuoka M. 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. Ther Adv Med Oncol 2010;2:301-7.
  • 3 Tsao AS, Papadimitrakopoulou VA. The future of NSCLC: Molecular profiles guiding treatment decisions. Oncology (Williston Park) 2011;25:607, 614.
  • 4 Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007;448:561-6.
  • 5 Zhang X, Zhang S, Yang X, Yang J, Zhou Q, Yin L, et al. Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression. Mol Cancer 2010;9:188.
  • 6 Sequist LV, Heist RS, Shaw AT, Fidias P, Rosovsky R, Temel JS, et al. Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice. Ann Oncol 2011;22:2616-24.
  • 7 Kris MG, Johnson BE, Kwiatkowski DJ. Identification of driver mutations in tumor specimens from 1,000 patients with lung adenocarcinoma: the NCI's Lung Cancer Mutation Consortium (LCMC). J ClinOncol 2011;29:Abstr CRA7506.
  • 8 Sahoo R, Harini VV, Babu VC, Patil Okaly GV, Rao S, Nargund A, et al. Screening for EGFR mutations in lung cancer, a report from India. Lung Cancer 2011;73:316-9.
  • 9 Chougule A, Prabhash K, Noronha V, Joshi A, Thavamani A, Chandrani P, et al. Frequency of EGFR mutations in 907 lung adenocarcinoma patients of Indian ethnicity. PLoS One 2013;8:e76164.
  • 10 Doval DC, Azam S, Batra U, Choudhury KD, Talwar V, Gupta SK, et al. Epidermal growth factor receptor mutation in lung adenocarcinoma in India: A single center study. J Carcinog 2013;12:12.
  • 11 Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129-39.
  • 12 Cortes-Funes H, Gomez C, Rosell R, Valero P, Garcia-Giron C, Velasco A, et al. Epidermal growth factor receptor activating mutations in Spanish gefitinib-treated non-small-cell lung cancer patients. Ann Oncol 2005;16:1081-6.
  • 13 Wu SG, Gow CH, Yu CJ, Chang YL, Yang CH, Hsu YC, et al. Frequent epidermal growth factor receptor gene mutations in malignant pleural effusion of lung adenocarcinoma. Eur Respir J 2008;32:924-30.
  • 14 Usui K, Ushijima T, Tanaka Y, Tanai C, Noda H, Abe N, et al. The frequency of epidermal growth factor receptor mutation of nonsmall cell lung cancer according to the underlying pulmonary diseases. Pulm Med 2011;2011:290132.
  • 15 Huang YS, Yang JJ, Zhang XC, Yang XN, Huang YJ, Xu CR, et al. Impact of smoking status and pathologic type on epidermal growth factor receptor mutations in lung cancer. Chin Med J (Engl) 2011;124:2457-60.
  • 16 Kim DW, Ahn MJ, Shi Y, Yang PC, Liu X, De Pas TM, et al. Updated results of a global phase II study with Crizotinib in advanced ALK-positive Non-Small Cell Lung Cancer (NSCLC). Ann Oncol 2012; 23:Abstr 1230 PD.
  • 17 Wong DW, Leung EL, So KK, Tam IY, Sihoe AD, Cheng LC, et al. The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer 2009;115:1723-33.
  • 18 Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010;363:1693-703.
  • 19 Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013;368:2385-94.
  • 20 Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Iafrate AJ, Shapiro G, et al. Impact of crizotinib on survival in patients with advanced, ALK positive NSCLC compared with historical controls. J Clin Oncol 29: 2011 (Suppl; abstr7507).
  • 21 Marchetti A, Di Lorito A, Pace MV, Iezzi M, Felicioni L, D'Antuono T, et al. 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. J Thorac Oncol 2016;11:487-95.
  • 22 von Laffert M, Warth A, Penzel R, Schirmacher P, Kerr KM, Elmberger G, et al. Multicenter immunohistochemical ALK-testing of non-small-cell lung cancer shows high concordance after harmonization of techniques and interpretation criteria. J Thorac Oncol 2014;9:1685-92.
  • 23 Pekar-Zlotin M, Hirsch FR, Soussan-Gutman L, Ilouze M, Dvir A, Boyle T, et al. Fluorescence in situ hybridization, immunohistochemistry, and next-generation sequencing for detection of EML4-ALK rearrangement in lung cancer. Oncologist 2015;20:316-22.
  • 24 Shaw AT, Engelman JA. ALK in lung cancer: Past, present, and future. J Clin Oncol 2013;31:1105-11.
  • 25 Desai SS, Shah AS, Prabhash K, Jambhekar NA. A year of anaplastic large cell kinase testing for lung carcinoma: Pathological and technical perspectives. Indian J Cancer 2013;50:80-6.
  • 26 Doval D, Prabhash K, Patil S, Chaturvedi H, Goswami C, Vaid A, et al. Clinical and epidemiological study of EGFR mutations and EML4-ALK fusion genes among indian patients with adenocarcinoma of the lung. Onco Targets Ther 2015;8:117-23.
  • 27 Mehta A, Batra U. Molecular epidemiological study of microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene using immunohistochemistry as a cost effective alternative to fluorescence in situ hybridization for Indian patients with adenocarcinoma lung. Asian J Oncol 2017;3:45-9.
  • 28 Wang M, Wang G, Ma H, Shan B. Crizotinib versus chemotherapy on ALK-positive NSCLC: A systematic review of efficacy and safety. Curr Cancer Drug Targets. 2017 Jun 23. [Epub ahead of print] PubMed PMID: 28669346.
  • 29 Wallander ML, Geiersbach KB, Tripp SR, Layfield LJ. 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. Arch Pathol Lab Med 2012;136:796-803.
  • 30 Ma D, Wang Z, Yang L, Mu X, Wang Y, Zhao X, et al. Responses to crizotinib in patients with ALK-positive lung adenocarcinoma who tested immunohistochemistry (IHC)-positive and fluorescence in situ hybridization (FISH)-negative. Oncotarget 2016;7:64410-20.
  • 31 Ying J, Guo L, Qiu T, Shan L, Ling Y, Liu X, et al. Diagnostic value of a novel fully automated immunochemistry assay for detection of ALK rearrangement in primary lung adenocarcinoma. Ann Oncol 2013;24:2589-93.
  • 32 Lantuejoul S, Rouquette I, Blons H, Le Stang N, Ilie M, Begueret H, et al. French multicentric validation of ALK rearrangement diagnostic in 547 lung adenocarcinomas. Eur Respir J 2015;46:207-18.
  • 33 McLeer-Florin A, Moro-Sibilot D, Melis A, Salameire D, Lefebvre C, Ceccaldi F, et al. Dual IHC and FISH testing for ALK gene rearrangement in lung adenocarcinomas in a routine practice: A French study. J Thorac Oncol 2012;7:348-54.
  • 34 Paik JH, Choe G, Kim H, Choe JY, Lee HJ, Lee CT, et al. Screening of anaplastic lymphoma kinase rearrangement by immunohistochemistry in non-small cell lung cancer: Correlation with fluorescence in situ hybridization. J Thorac Oncol 2011;6:466-72.
  • 35 Thunnissen E, Bubendorf L, Dietel M, Elmberger G, Kerr K, Lopez-Rios F, et al. EML4-ALK testing in non-small cell carcinomas of the lung: A review with recommendations. Virchows Arch 2012;461:245-57.
  • 36 Ali SM, Hensing T, Schrock AB, Allen J, Sanford E, Gowen K, et al. Comprehensive genomic profiling identifies a subset of crizotinib-responsive ALK-rearranged non-small cell lung cancer not detected by fluorescence in situ hybridization. Oncologist 2016;21:762-70.