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      • Record: found
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      Does ALK-rearrangement predict favorable response to the therapy of bevacizumab plus pemetrexed in advanced non-small-cell lung cancer? Case report and literature review

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          Abstract

          Background

          Advanced ALK-rearranged non-small cell lung cancer (NSCLC) patients will develop acquired resistance after anaplastic lymphoma kinase (ALK) inhibitors therapies. Vascular endothelial growth factor-A (VEGF-A) production and tumor vessel formation were found to be more significantly enriched in ALK-rearrangement NSCLC than that in epidermal growth factor receptor or Kirsten rat sarcoma viral oncogene mutated NSCLC. However, the correlation between ALK rearrangement and the efficacy of bevacizumab (a recombinant humanized IgG1 monoclonal antibody targeting VEGF-A) was still elusive.

          Case presentation

          We report a case with metastatic NSCLC harboring ALK-rearrangement who was initially resistant to two courses of ALK-Tyrosine Kinase Inhibitor (TKI) therapy, but got a clinical benefit of 7 months of progression free survival after the combined treatment of bevacizumab plus pemetrexed. And the patient tolerated well.

          Conclusions

          It suggested that bevacizumab combined with pemetrexed might be a preferred option for ALK rearrangement patient who had failed no less than two courses of ALK-TKIs.

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          Most cited references39

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          Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK.

          Alice Shaw, Beow Yeap, Mari Mino-Kenudson … (2009)
          The EML4-ALK fusion oncogene represents a novel molecular target in a small subset of non-small-cell lung cancers (NSCLC). To aid in identification and treatment of these patients, we examined the clinical characteristics and treatment outcomes of patients who had NSCLC with and without EML4-ALK. Patients with NSCLC were selected for genetic screening on the basis of two or more of the following characteristics: female sex, Asian ethnicity, never/light smoking history, and adenocarcinoma histology. EML4-ALK was identified by using fluorescent in situ hybridization for ALK rearrangements and was confirmed by immunohistochemistry for ALK expression. EGFR and KRAS mutations were determined by DNA sequencing. Of 141 tumors screened, 19 (13%) were EML4-ALK mutant, 31 (22%) were EGFR mutant, and 91 (65%) were wild type (WT/WT) for both ALK and EGFR. Compared with the EGFR mutant and WT/WT cohorts, patients with EML4-ALK mutant tumors were significantly younger (P < .001 and P = .005) and were more likely to be men (P = .036 and P = .039). Patients with EML4-ALK-positive tumors, like patients who harbored EGFR mutations, also were more likely to be never/light smokers compared with patients in the WT/WT cohort (P < .001). Eighteen of the 19 EML4-ALK tumors were adenocarcinomas, predominantly the signet ring cell subtype. Among patients with metastatic disease, EML4-ALK positivity was associated with resistance to EGFR tyrosine kinase inhibitors (TKIs). Patients in the EML4-ALK cohort and the WT/WT cohort showed similar response rates to platinum-based combination chemotherapy and no difference in overall survival. EML4-ALK defines a molecular subset of NSCLC with distinct clinical characteristics. Patients who harbor this mutation do not benefit from EGFR TKIs and should be directed to trials of ALK-targeted agents.
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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

            Maximillian Hochmair, Fabrice Branle, Serafino Pantano … (2017)
            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 in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study.

              Sai-Hong Ignatius Ou, Jin Seok Ahn, Luigi De Petris … (2016)
              Crizotinib confers improved progression-free survival compared with chemotherapy in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC), but progression invariably occurs. We investigated the efficacy and safety of alectinib, a potent and selective ALK inhibitor with excellent CNS penetration, in patients with crizotinib-refractory ALK-positive NSCLC.
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                Author and article information

                Contributors
                Zhichao Liu: zhichaoliu1990@163.com
                Youting Bao: 648858660@qq.com
                Butuo Li: libutuo01761990@163.com
                Xindong Sun: sunxindongjn@163.com
                Linlin Wang:
                ORCID: http://orcid.org/0000-0002-2873-4204
                wanglinlinatjn@163.com
                Journal
                Journal ID (nlm-ta): Clin Transl Med
                Journal ID (iso-abbrev): Clin Transl Med
                Title: Clinical and Translational Medicine
                Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )
                ISSN (Electronic): 2001-1326
                Publication date (Electronic): 9 January 2018
                Publication date PMC-release: 9 January 2018
                Publication date Collection: 2018
                Volume: 7
                Electronic Location Identifier: 1
                Affiliations
                [1 ]GRID grid.410587.f, School of Medicine and Life Sciences, , University of Jinan-Shandong Academy of Medical Sciences, ; Jinan, 250200 China
                [2 ]GRID grid.410587.f, Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, , Shandong Academy of Medical Science, ; No. 440, Ji Yan Road, Jinan, 250017 Shandong China
                [3 ]ISNI 0000 0004 1790 6079, GRID grid.268079.2, Clinical College, , Weifang Medical University, ; Weifang, 261053 China
                Author information
                http://orcid.org/0000-0002-2873-4204
                Article
                Publisher ID: 178
                DOI: 10.1186/s40169-017-0178-x
                PMC ID: 5760484
                PubMed ID: 29318404
                SO-VID: 1b19b2d6-58b6-4ba7-8267-adf52c3be8d6
                Copyright © © The Author(s) 2018
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Date received : 3 October 2017
                Date accepted : 22 December 2017
                Funding
                Funded by: Natural Science Foundation of Shandong Province (CN)
                Award ID: ZR2016HM41
                Award Recipient :
                Funded by: The Project of the National Natural Science Foundation of China
                Award ID: 81402299
                Award ID: 81472812
                Award Recipient :
                Funded by: The Project of Postdoctoral Innovation of Shandong Province
                Award ID: 201501010
                Award ID: 201601006
                Funded by: The Project of Postdoctoral Science Foundation of China
                Award ID: 2016M590640
                Award Recipient :
                Categories
                Subject: Case Report
                Custom metadata
                issue-copyright-statement © The Author(s) 2018

                ScienceOpen disciplines: Medicine
                Keywords: alk,alk inhibitor resistance,non-small cell lung cancer,pemetrexed,bevacizumab
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: alk, alk inhibitor resistance, non-small cell lung cancer, pemetrexed, bevacizumab

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