Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives

Etienne Giroux Leprieur,1,2 Vincent Fallet,3,4 Jacques Cadranel,3,4 Marie Wislez3,4 1Respiratory Diseases and Thoracic Oncology Department, APHP-Ambroise Paré Hospital, Boulogne-Billancourt, France; 2EA4340 Laboratory, UVSQ, Paris-Saclay University, France; 3Respiratory Diseases Departmen...

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Autores principales:	Giroux Leprieur E, Fallet V, Cadranel J, Wislez M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	ALK rearrangement crizotinib non-small cell lung carcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/2059dbbae5964960a6fa029619e4506f
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spelling	oai:doaj.org-article:2059dbbae5964960a6fa029619e4506f2021-12-02T03:14:06ZSpotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives1179-2728https://doaj.org/article/2059dbbae5964960a6fa029619e4506f2016-06-01T00:00:00Zhttps://www.dovepress.com/spotlight-on-crizotinib-in-the-first-line-treatment-of-alk-positive-ad-peer-reviewed-article-LCTThttps://doaj.org/toc/1179-2728Etienne Giroux Leprieur,1,2 Vincent Fallet,3,4 Jacques Cadranel,3,4 Marie Wislez3,4 1Respiratory Diseases and Thoracic Oncology Department, APHP-Ambroise Paré Hospital, Boulogne-Billancourt, France; 2EA4340 Laboratory, UVSQ, Paris-Saclay University, France; 3Respiratory Diseases Department, APHP – Tenon Hospital, Paris, France; 4Sorbonne University, GRC 04, UPMC Univ Paris 06, France Abstract: Around 4% of advanced non-small-cell lung cancers (NSCLCs) have an ALK rearrangement at the time of diagnosis. This molecular feature is more frequent in young patients, with no/light smoking habit and with adenocarcinoma pathological subtype. Crizotinib is a tyrosine kinase inhibitor, targeting ALK, ROS1, RON, and MET. The preclinical efficacy results led to a fast-track clinical development. The US Food and Drug Administration (FDA) approval was achieved after the Phase I clinical trial in 2011 in ALK-rearranged advanced NSCLC progressing after a first-line treatment. In 2013, the randomized Phase III trial PROFILE-1007 confirmed the efficacy of crizotinib in ALK-rearranged NSCLC, compared to cytotoxic chemotherapy, in second-line setting or more. In 2014, the PROFILE-1014 trial showed the superiority of crizotinib in the first-line setting compared to the pemetrexed platinum doublet chemotherapy. The response rate was 74%, and the progression-free survival was 10.9 months with crizotinib. Based on these results, crizotinib received approval from the FDA and European Medicines Agency for first-line treatment of ALK-rearranged NSCLC. The various molecular mechanisms at the time of the progression (ALK mutations or amplification, ALK-independent mechanisms) encourage performing re-biopsy at the time of progression under crizotinib. The best treatment strategy at the progression (crizotinib continuation beyond progression, switch to second-generation tyrosine kinase inhibitors, or cytotoxic chemotherapy) depends on the phenotype of the progression, the molecular status, and the physical condition of the patient. Keywords: ALK rearrangement, crizotinib, non-small-cell lung carcinomaGiroux Leprieur EFallet VCadranel JWislez MDove Medical PressarticleALK rearrangementcrizotinibnon-small cell lung carcinomaNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol 2016, Iss Issue 1, Pp 83-90 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	ALK rearrangement crizotinib non-small cell lung carcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	ALK rearrangement crizotinib non-small cell lung carcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Giroux Leprieur E Fallet V Cadranel J Wislez M Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives
description	Etienne Giroux Leprieur,1,2 Vincent Fallet,3,4 Jacques Cadranel,3,4 Marie Wislez3,4 1Respiratory Diseases and Thoracic Oncology Department, APHP-Ambroise Paré Hospital, Boulogne-Billancourt, France; 2EA4340 Laboratory, UVSQ, Paris-Saclay University, France; 3Respiratory Diseases Department, APHP – Tenon Hospital, Paris, France; 4Sorbonne University, GRC 04, UPMC Univ Paris 06, France Abstract: Around 4% of advanced non-small-cell lung cancers (NSCLCs) have an ALK rearrangement at the time of diagnosis. This molecular feature is more frequent in young patients, with no/light smoking habit and with adenocarcinoma pathological subtype. Crizotinib is a tyrosine kinase inhibitor, targeting ALK, ROS1, RON, and MET. The preclinical efficacy results led to a fast-track clinical development. The US Food and Drug Administration (FDA) approval was achieved after the Phase I clinical trial in 2011 in ALK-rearranged advanced NSCLC progressing after a first-line treatment. In 2013, the randomized Phase III trial PROFILE-1007 confirmed the efficacy of crizotinib in ALK-rearranged NSCLC, compared to cytotoxic chemotherapy, in second-line setting or more. In 2014, the PROFILE-1014 trial showed the superiority of crizotinib in the first-line setting compared to the pemetrexed platinum doublet chemotherapy. The response rate was 74%, and the progression-free survival was 10.9 months with crizotinib. Based on these results, crizotinib received approval from the FDA and European Medicines Agency for first-line treatment of ALK-rearranged NSCLC. The various molecular mechanisms at the time of the progression (ALK mutations or amplification, ALK-independent mechanisms) encourage performing re-biopsy at the time of progression under crizotinib. The best treatment strategy at the progression (crizotinib continuation beyond progression, switch to second-generation tyrosine kinase inhibitors, or cytotoxic chemotherapy) depends on the phenotype of the progression, the molecular status, and the physical condition of the patient. Keywords: ALK rearrangement, crizotinib, non-small-cell lung carcinoma
format	article
author	Giroux Leprieur E Fallet V Cadranel J Wislez M
author_facet	Giroux Leprieur E Fallet V Cadranel J Wislez M
author_sort	Giroux Leprieur E
title	Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives
title_short	Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives
title_full	Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives
title_fullStr	Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives
title_full_unstemmed	Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives
title_sort	spotlight on crizotinib in the first-line treatment of alk-positive advanced non-small-cell lung cancer: patients selection and perspectives
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/2059dbbae5964960a6fa029619e4506f
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Spotlight on crizotinib in the first-line treatment of ALK-positive advanced non-small-cell lung cancer: patients selection and perspectives

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