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      Brain Metastases in Oncogene-Addicted Non-Small Cell Lung Cancer Patients: Incidence and Treatment

      review-article
      1 , * , 2 , 3 , *
      Frontiers in Oncology
      Frontiers Media S.A.
      brain, metastases, non-small cell lung cancer, EGFR, ALK

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          Abstract

          Brain metastases (BM) are common in non-small cell lung cancer patients including in molecularly selected populations, such as EGFR-mutant and ALK-rearranged tumors. They are associated with a reduced quality of life, and are commonly the first site of progression for patients receiving tyrosine kinase inhibitors (TKIs). In this review, we summarize incidence of BM and intracranial efficacy with TKI agents according to oncogene driver mutations, focusing on important clinical issues, notably optimal first-line treatment in oncogene-addicted lung tumors with upfront BM (local therapies followed by TKI vs. TKI monotherapy). We also discuss the potential role of newly emerging late-generation TKIs as new standard treatment in oncogene-addicted lung cancer tumors compared with sequential strategies.

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          Most cited references118

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          First-line ceritinib versus platinum-based chemotherapy in advanced ALK -rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study

          The efficacy of ceritinib in patients with untreated anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is not known. We assessed the efficacy and safety of ceritinib versus platinum-based chemotherapy in these patients.
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            Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial.

            Alectinib, a potent, highly selective, CNS-active inhibitor of anaplastic lymphoma kinase (ALK), showed promising efficacy and tolerability in the single-arm phase 1/2 AF-001JP trial in Japanese patients with ALK-positive non-small-cell lung cancer. Given those promising results, we did a phase 3 trial to directly compare the efficacy and safety of alectinib and crizotinib.
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              Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity.

              Approximately one-third of patients with non-small cell lung cancer (NSCLC) harboring tumors with EGFR-tyrosine kinase inhibitor (TKI)-sensitizing mutations (EGFRm) experience disease progression during treatment due to brain metastases. Despite anecdotal reports of EGFR-TKIs providing benefit in some patients with EGFRm NSCLC brain metastases, there is a clinical need for novel EGFR-TKIs with improved efficacy against brain lesions.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                11 April 2018
                2018
                : 8
                : 88
                Affiliations
                [1] 1Medical Oncology Department, Hospital Universitari Vall d’Hebron , Barcelona, Spain
                [2] 2Cancer Medicine Department, Institut Gustave Roussy , Villejuif, France
                [3] 3University Paris-Sud , Orsay, France
                Author notes

                Edited by: Marco Lucchi, Università degli Studi di Pisa, Italy

                Reviewed by: Minesh P. Mehta, Baptist Health South Florida, United States; Emilio Bria, University of Verona, Italy

                *Correspondence: J. Remon, jremon@ 123456vhio.net ; Benjamin Besse, benjamin.besse@ 123456gustaveroussy.fr

                Specialty section: This article was submitted to Thoracic Oncology, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2018.00088
                5904204
                29696132
                71cf630d-dda7-4d4a-b99c-f87de68075f3
                Copyright © 2018 Remon and Besse.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 December 2017
                : 14 March 2018
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 147, Pages: 15, Words: 14456
                Categories
                Oncology
                Review

                Oncology & Radiotherapy
                brain,metastases,non-small cell lung cancer,egfr,alk
                Oncology & Radiotherapy
                brain, metastases, non-small cell lung cancer, egfr, alk

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