1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Sequential therapy according to distinct disease progression patterns in advanced ALK-positive non-small-cell lung cancer after crizotinib treatment

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective

          Crizotinib is recommended as the first-line therapy for advanced anaplastic lymphoma kinase ( ALK)-positive non-small-cell lung cancer (NSCLC). Despite its initial efficacy, patients ultimately acquire resistance to crizotinib within 1 year. In such patients, the optimal sequential therapy after crizotinib treatment remains unknown. This study explored which sequential therapy option confers the greatest benefit.

          Methods

          A total of 138 patients with advanced ALK-positive NSCLC resistant to crizotinib were studied. Based on patterns of disease progression of metastases, patients were divided into 3 groups: brain progression, non-liver progression, and liver progression. Sequential therapies included crizotinib continuation plus local therapy, next-generation ALK inhibitors (ALKi’s), and chemotherapy. The primary endpoint was overall survival (OS) from the time of crizotinib resistance to death or last follow-up.

          Results

          The 138 patients included 64 cases with progression in brain, 57 cases in non-liver sites and 17 cases in liver. A significant difference in OS was observed among the distinct progression pattern (median OS, 25.4 months in brain, 15.8 months in non-liver, and 10.8 months in liver, respectively, P=0.020). The difference in OS among sequential therapies was statistically significant in the non-liver progression group (median OS, 27.6 months with next-generation ALKi’s, 13.3 months with crizotinib continuation, and 10.8 months with chemotherapy, respectively, P=0.019). However, crizotinib continuation plus local therapy seems to provide non-inferior median OS compared with next-generation ALKi’s for patients with brain progression (median OS, 28.9 months vs. 32.8 months, P=0.204). And no significant differences in OS were found in patients with progression in liver (P=0.061).

          Conclusions

          Crizotinib continuation together with local therapy might be a feasible strategy for patients with progression in brain beyond crizotinib resistance, as well as next-generation ALKi’s. Next-generation ALKi’s tended to provide a survival benefit in patients with non-liver progression.

          Related collections

          Most cited references14

          • Record: found
          • Abstract: not found
          • Article: not found

          CSF concentration of the anaplastic lymphoma kinase inhibitor crizotinib.

            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The biology and treatment of EML4-ALK non-small cell lung cancer.

            The fusion between echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) has recently been identified in a subset of non-small cell lung cancers (NSCLCs). EML4-ALK is most often detected in never smokers with lung cancer and has unique pathologic features. EML4-ALK is oncogenic both in vitro and in vivo and ALK kinase inhibitors are quite effective in pre-clinical model systems. More recently ALK inhibitors have entered clinical development and remarkably clinical efficacy has been observed in NSCLC patients harbouring EML4-ALK translocations. This review will focus on the biology, clinical characteristics, diagnosis and treatment of EML4-ALK NSCLC. Copyright 2010 Elsevier Ltd. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              ALK in lung cancer: past, present, and future.

              In 2007, scientists discovered that anaplastic lymphoma kinase (ALK) gene rearrangements are present in a small subset of non-small-cell lung cancers. ALK-positive cancers are highly sensitive to small-molecule ALK kinase inhibitors, such as crizotinib. Phase I and II studies of crizotinib in ALK-positive lung cancer demonstrated impressive activity and clinical benefit, leading to rapid US Food and Drug Administration approval in 2011. Although crizotinib induces remissions and extends the lives of patients, cures are not achieved as resistance to therapy develops. In this review, we will discuss the history of this field, current diagnostic and treatment practices, and future challenges and opportunities to advance outcomes for patients with ALK-positive lung cancers.
                Bookmark

                Author and article information

                Contributors
                Journal
                Chin J Cancer Res
                Chin. J. Cancer Res
                CJCR
                Chinese Journal of Cancer Research
                AME Publishing Company
                1000-9604
                1993-0631
                April 2019
                : 31
                : 2
                : 349-356
                Affiliations
                [1 ] Department of Comprehensive Oncology
                [2 ] Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
                Author notes
                Yan Wang. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China. Email: wangyanyifu@ 123456163.com
                Article
                cjcr-31-2-349
                10.21147/j.issn.1000-9604.2019.02.09
                6513749
                935c9148-221d-450d-ae4e-70ee2a8322d8
                Copyright © 2019 Chinese Journal of Cancer Research. All rights reserved.

                This work is licensed under a Creative Commons Attribution-Non Commercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

                History
                : 14 November 2018
                : 8 March 2019
                Categories
                Original Article

                alk,crizotinib,non-small-cell lung cancer,resistance,sequential therapy

                Comments

                Comment on this article