56
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Is there a progression‐free survival benefit of first‐line crizotinib versus standard chemotherapy and second‐line crizotinib in ALK‐positive advanced lung adenocarcinoma? A retrospective study of Chinese patients

      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

          Although crizotinib has demonstrated promising efficacy and acceptable toxicity in patients with advanced non‐small cell lung cancer ( NSCLC), the available evidence in Chinese populations is currently limited. This study compared the progression‐free survival ( PFS) of Chinese patients with anaplastic lymphoma kinase ( ALK )‐positive, advanced lung adenocarcinoma who received first‐line crizotinib therapy with that of patients who received first‐line standard chemotherapy, and also the PFS benefit of first‐line versus second‐line crizotinib treatment. Data on 80 patients with ALK ‐positive, advanced lung adenocarcinoma who received crizotinib or standard chemotherapy as first‐line treatments between June 2013 and December 2014 were retrospectively collected; 26 of the patients received crizotinib as second‐line therapy after progressive disease ( PD) occurred on first‐line chemotherapy. Tumor responses were assessed using Response Evaluation Criteria in Solid Tumors ( RECIST), version 1.1. The median PFS was 13.3 months (95% CI: 6.5–20.0 months) in patients who received first‐line crizotinib as compared with 5.4 months (95% CI: 4.4–6.5 months) in patients who received first‐line standard chemotherapy (adjusted hazard ratio for progression or death with crizotinib, 0.20; 95% CI: 0.11–0.36; < 0.001). In patients who received second‐line crizotinib therapy, the median PFS was 9.9 months (95% CI: 6.4–13.4 months). The difference between first‐line and second‐line crizotinib treatment was not statistically significant (adjusted hazard ratio for progression, 0.56; 95% CI: 0.29–1.11; = 0.092). Thus, there was a significant PFS benefit of first‐line crizotinib versus first‐line standard chemotherapy in Chinese patients with ALK ‐positive lung adenocarcinoma. Additionally, crizotinib showed promising efficacy in patients who received it as second‐line therapy after PD had occurred on first‐line chemotherapy.

          Related collections

          Most cited references11

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

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

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

            ROS1 rearrangements define a unique molecular class of lung cancers.

            Chromosomal rearrangements involving the ROS1 receptor tyrosine kinase gene have recently been described in a subset of non-small-cell lung cancers (NSCLCs). Because little is known about these tumors, we examined the clinical characteristics and treatment outcomes of patients with NSCLC with ROS1 rearrangement. Using a ROS1 fluorescent in situ hybridization (FISH) assay, we screened 1,073 patients with NSCLC and correlated ROS1 rearrangement status with clinical characteristics, overall survival, and when available, ALK rearrangement status. In vitro studies assessed the responsiveness of cells with ROS1 rearrangement to the tyrosine kinase inhibitor crizotinib. The clinical response of one patient with ROS1-rearranged NSCLC to crizotinib was investigated as part of an expanded phase I cohort. Of 1,073 tumors screened, 18 (1.7%) were ROS1 rearranged by FISH, and 31 (2.9%) were ALK rearranged. Compared with the ROS1-negative group, patients with ROS1 rearrangements were significantly younger and more likely to be never-smokers (each P < .001). All of the ROS1-positive tumors were adenocarcinomas, with a tendency toward higher grade. ROS1-positive and -negative groups showed no difference in overall survival. The HCC78 ROS1-rearranged NSCLC cell line and 293 cells transfected with CD74-ROS1 showed evidence of sensitivity to crizotinib. The patient treated with crizotinib showed tumor shrinkage, with a near complete response. ROS1 rearrangement defines a molecular subset of NSCLC with distinct clinical characteristics that are similar to those observed in patients with ALK-rearranged NSCLC. Crizotinib shows in vitro activity and early evidence of clinical activity in ROS1-rearranged NSCLC.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Activity of crizotinib (PF02341066), a dual mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK) inhibitor, in a non-small cell lung cancer patient with de novo MET amplification.

              Crizotinib is a dual MET and ALK inhibitor. Currently, clinical development of crizotinib is focused primarily on ALK rearranged non-small cell lung cancer (NSCLC). Here we report an NSCLC patient with de novo MET amplification but no ALK rearrangement who achieved a rapid and durable response to crizotinib indicating is also a bona fide MET inhibitor.
                Bookmark

                Author and article information

                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                16 February 2016
                June 2016
                : 5
                : 6 ( doiID: 10.1002/cam4.2016.5.issue-6 )
                : 1013-1021
                Affiliations
                [ 1 ] Department of Pulmonary MedicineShanghai Chest Hospital Shanghai Jiao Tong University ShanghaiChina
                Author notes
                [*] [* ] Correspondence

                Liyan Jiang, Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241# HuaiHai (W.) Rd, Shanghai 200030, China. Tel: +86 13916146759; Fax: +86 021‐32260856; E‐mail: Jiang_liyan2000@ 123456126.com

                Article
                CAM4659
                10.1002/cam4.659
                4924358
                26880708
                fbc57d14-411f-4275-9f33-4dceb1b85889
                © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 October 2015
                : 03 January 2016
                : 12 January 2016
                Page count
                Pages: 9
                Categories
                Original Research
                Clinical Cancer Research
                Original Research
                Custom metadata
                2.0
                cam4659
                June 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.1 mode:remove_FC converted:28.06.2016

                Oncology & Radiotherapy
                anaplastic lymphoma kinase,crizotinib,first‐line chemotherapy,lung adenocarcinoma,progression‐free survival

                Comments

                Comment on this article