Incidence of ROS1-Rearranged Non-Small-Cell Lung Carcinoma in India and Efficacy of Crizotinib in Lung Adenocarcinoma Patients
Anurag Mehta, 1 Mumtaz Saifi, 2 Ullas Batra, 3 M Suryavanshi, 2 Kush Gupta 4 1Laboratory Services, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India; 2Department of Molecular Pathology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India; 3Medical Oncology, Rajiv...
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Dove Medical Press
2020
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oai:doaj.org-article:399af9303b5a4cea8b3c79464c26f7a12021-12-02T00:55:49ZIncidence of ROS1-Rearranged Non-Small-Cell Lung Carcinoma in India and Efficacy of Crizotinib in Lung Adenocarcinoma Patients1179-2728https://doaj.org/article/399af9303b5a4cea8b3c79464c26f7a12020-02-01T00:00:00Zhttps://www.dovepress.com/incidence-of-ros1-rearranged-non-small-cell-lung-carcinoma-in-india-an-peer-reviewed-article-LCTThttps://doaj.org/toc/1179-2728Anurag Mehta, 1 Mumtaz Saifi, 2 Ullas Batra, 3 M Suryavanshi, 2 Kush Gupta 4 1Laboratory Services, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India; 2Department of Molecular Pathology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India; 3Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India; 4Catalyst Clinical Services, New Delhi, IndiaCorrespondence: Anurag MehtaLaboratory Services, Rajiv Gandhi Cancer Institute and Research Centre, Sector V, Rohini, New Delhi 110085 Tel +91 9868 020 371Email anumehta11@gmail.comBackground: The ROS1 gene is a member of the “sevenless” subfamily of tyrosine-kinase insulin-receptor genes. ROS1-fusion rearrangement causes constitutive downstream signal transduction, with an oncogenic role in non-small-cell lung carcinoma (NSCLC). Fortunately, crizotinib, an ALK1 tyrosine-kinase inhibitor, provides long-term disease control. The objective of this molecular epidemiological study was to estimate the frequency of ROS1 rearrangements and evaluate treatment outcomes with crizotinib therapy.Methods: Patients with stage IV NSCLC adenocarcinoma histology were considered for this study. The study was conducted according to the ethical principles stated in the latest version of the Declaration of Helsinki and the applicable guidelines for good clinical practice. Clinical characteristics and treatment details were collected from patients’ medical records.Results: A total of 709 stage IV NSCLC adenocarcinoma patients were included in the study. There were 457 (64.46%) men and 252 (35.54%) women, with a median age of 60 years. ROS1-gene rearrangement was positive in 20 (2.82%) cases, 13 using Fluorescent In-Situ Hybridization (FISH), and two and five cases, respectively, using immunohistochemistry (IHC) and next-generation sequencing (NGS), followed by confirmation with FISH. Fourteen of the 20 patients with ROS1-gene rearrangement received crizotinib therapy, with an objective response rate of 64.28%. At a median follow-up of 6 months, the study had not achieved the end points of median progression free survival and overall survival.Conclusion: ROS1-gene rearrangement was present at a relatively higher frequency of 2.8% in north Indian patients with lung adenocarcinoma and was successfully targeted by crizotinib therapy. Although the only US Food and Drug Administration and Conformité Européenne approved method for testing ROS1 rearrangement is NGS, FISH alone or IHC with D4D6 antibody as initial screen with subsequent confirmation of IHC-positive cases by FISH are cost-effective methods in institutions lacking NGS facilities.Keywords: NSCLC, ROS1, crizotinibMehta ASaifi MBatra USuryavanshi MGupta KDove Medical Pressarticlensclcros 1crizotinibNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol Volume 11, Pp 19-25 (2020) |
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nsclc ros 1 crizotinib Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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nsclc ros 1 crizotinib Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Mehta A Saifi M Batra U Suryavanshi M Gupta K Incidence of ROS1-Rearranged Non-Small-Cell Lung Carcinoma in India and Efficacy of Crizotinib in Lung Adenocarcinoma Patients |
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Anurag Mehta, 1 Mumtaz Saifi, 2 Ullas Batra, 3 M Suryavanshi, 2 Kush Gupta 4 1Laboratory Services, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India; 2Department of Molecular Pathology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India; 3Medical Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India; 4Catalyst Clinical Services, New Delhi, IndiaCorrespondence: Anurag MehtaLaboratory Services, Rajiv Gandhi Cancer Institute and Research Centre, Sector V, Rohini, New Delhi 110085 Tel +91 9868 020 371Email anumehta11@gmail.comBackground: The ROS1 gene is a member of the “sevenless” subfamily of tyrosine-kinase insulin-receptor genes. ROS1-fusion rearrangement causes constitutive downstream signal transduction, with an oncogenic role in non-small-cell lung carcinoma (NSCLC). Fortunately, crizotinib, an ALK1 tyrosine-kinase inhibitor, provides long-term disease control. The objective of this molecular epidemiological study was to estimate the frequency of ROS1 rearrangements and evaluate treatment outcomes with crizotinib therapy.Methods: Patients with stage IV NSCLC adenocarcinoma histology were considered for this study. The study was conducted according to the ethical principles stated in the latest version of the Declaration of Helsinki and the applicable guidelines for good clinical practice. Clinical characteristics and treatment details were collected from patients’ medical records.Results: A total of 709 stage IV NSCLC adenocarcinoma patients were included in the study. There were 457 (64.46%) men and 252 (35.54%) women, with a median age of 60 years. ROS1-gene rearrangement was positive in 20 (2.82%) cases, 13 using Fluorescent In-Situ Hybridization (FISH), and two and five cases, respectively, using immunohistochemistry (IHC) and next-generation sequencing (NGS), followed by confirmation with FISH. Fourteen of the 20 patients with ROS1-gene rearrangement received crizotinib therapy, with an objective response rate of 64.28%. At a median follow-up of 6 months, the study had not achieved the end points of median progression free survival and overall survival.Conclusion: ROS1-gene rearrangement was present at a relatively higher frequency of 2.8% in north Indian patients with lung adenocarcinoma and was successfully targeted by crizotinib therapy. Although the only US Food and Drug Administration and Conformité Européenne approved method for testing ROS1 rearrangement is NGS, FISH alone or IHC with D4D6 antibody as initial screen with subsequent confirmation of IHC-positive cases by FISH are cost-effective methods in institutions lacking NGS facilities.Keywords: NSCLC, ROS1, crizotinib |
format |
article |
author |
Mehta A Saifi M Batra U Suryavanshi M Gupta K |
author_facet |
Mehta A Saifi M Batra U Suryavanshi M Gupta K |
author_sort |
Mehta A |
title |
Incidence of ROS1-Rearranged Non-Small-Cell Lung Carcinoma in India and Efficacy of Crizotinib in Lung Adenocarcinoma Patients |
title_short |
Incidence of ROS1-Rearranged Non-Small-Cell Lung Carcinoma in India and Efficacy of Crizotinib in Lung Adenocarcinoma Patients |
title_full |
Incidence of ROS1-Rearranged Non-Small-Cell Lung Carcinoma in India and Efficacy of Crizotinib in Lung Adenocarcinoma Patients |
title_fullStr |
Incidence of ROS1-Rearranged Non-Small-Cell Lung Carcinoma in India and Efficacy of Crizotinib in Lung Adenocarcinoma Patients |
title_full_unstemmed |
Incidence of ROS1-Rearranged Non-Small-Cell Lung Carcinoma in India and Efficacy of Crizotinib in Lung Adenocarcinoma Patients |
title_sort |
incidence of ros1-rearranged non-small-cell lung carcinoma in india and efficacy of crizotinib in lung adenocarcinoma patients |
publisher |
Dove Medical Press |
publishDate |
2020 |
url |
https://doaj.org/article/399af9303b5a4cea8b3c79464c26f7a1 |
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