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      Is there a benefit of first- or second-line crizotinib in locally advanced or metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer? a meta-analysis

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          Abstract

          Background

          Crizotinib show a promising efficacy in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). However, differences in efficacy for first- and second-line crizotinib are unclear.

          Results

          The pooled overall response rate and progression-free survival were 65% and 9.38 months, respectively. In the subgroup analysis, first-line crizotinib showed a higher trend of overall response rate and longer trend of progression-free survival although there was no statistical difference between first-line and second-line crizotinib (74%, 11.28 months vs. 65%, 8.12 months, respectively; fixed effects model). Moreover, overall response rate between Asians and Caucasians were similar (67% and 66%, respectively; fixed effects model).

          Materials and Methods

          A comprehensive search of MEDLINE, EMBASE, WEB OF SCIENCE and the COCHRANE databases from their inception to February 2016 was performed to identify clinical trials in English-language journals. Pooled overall response rate, progression-free survival and differences between first- and second-line crizotinib were estimated. Moreover, overall response rate between Asians and Caucasians were also estimated.

          Conclusions

          First-line crizotinib may more effective than second-line crizotinib for patients with locally advanced or metastatic ALK-positive NSCLC.

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          Most cited references29

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          Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study.

          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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            Phase 2 prospective analysis of alectinib in ALK-positive, crizotinib-resistant non-small-cell lung cancer

            Summary Background Alectinib, a highly selective, central nervous system (CNS)-active anaplastic lymphoma kinase (ALK) inhibitor, demonstrated promising clinical activity in crizotinib-naïve and crizotinib-resistant ALK-positive non-small-cell lung cancer (NSCLC). This phase 2 study evaluated the safety and efficacy of alectinib in ALK-positive NSCLC patients who progressed on previous crizotinib. Methods This ongoing North American study (NCT01871805) enrolled patients with stage IIIB/IV ALK-positive NSCLC, who had progressed following crizotinib. Patients were treated with oral alectinib 600 mg twice daily until progression, death or withdrawal. Primary endpoint was overall response rate (ORR) by independent review committee (IRC) using RECIST v1.1. Secondary endpoints included progression-free survival (PFS), duration of response (DOR), intracranial ORR and DOR, safety, and patient-reported outcomes. The intent-to-treat population was used for efficacy and safety analyses, with the response evaluable population used for response endpoints. Findings A total of 87 patients were enrolled in the intent-to-treat population. All patients had received prior crizotinib therapy, and 64 patients (74%) had also received prior chemotherapy. Fifty-two patients (60%) had baseline CNS metastases, of whom 18 (35%) had received no prior brain radiation therapy. At the time of primary analysis (median follow-up 4.8 months), ORR by IRC was 48% (95% CI 36–60). Adverse events were predominantly grade 1 or 2, most commonly constipation, fatigue, myalgia and peripheral edema. The most common grade ≥3 AEs were changes in laboratory values, including increased blood creatine phosphokinase (in 8%, n=7), increased alanine aminotransferase (in 6% n=5), and increased aspartate aminotransferase (in 5% n=4). Interpretation Alectinib demonstrated clinical efficacy and was well tolerated in patients with ALK-positive NSCLC who had progressed on crizotinib. Alectinib was active in the CNS, as demonstrated by durable responses in the majority of crizotinib-resistant patients with CNS disease. Therefore, alectinib could be a suitable treatment for patients with ALK-positive disease who have progressed on crizotinib.
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              Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastasis.

              We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non-small-cell lung cancer (NSCLC) and brain metastasis.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                6 December 2016
                7 November 2016
                : 7
                : 49
                : 81090-81098
                Affiliations
                1 Department of Thoracic Surgery, Medical College of Nanchang University, Nanchang, 330006, China
                2 Department of Integrated Chinese and Western Medicine, Medical College of Nanchang University, Nanchang, 330006, China
                3 Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangdong, 510060, China
                4 Department of General Surgery, Medical College of Nanchang University, Nanchang, 330006, China
                5 Department of Thoracic Surgery, Medical College of Nanchang University, Jiangxi Province Tumor Hospital, Nanchang, 330006, China
                6 Department of Integrated Chinese and Western Medicine, Jiangxi Province People's Hospital, Nanchang, 330006, China
                Author notes
                Correspondence to: Yu Kang Kuang, kuangyukang@ 123456aim.com
                Article
                13191
                10.18632/oncotarget.13191
                5348378
                27835601
                73ee252b-028b-4f39-a464-113a55f9eea0
                Copyright: © 2016 Hu et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 23 April 2016
                : 31 October 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                meta-analysis,crizotinib,anaplastic lymphoma kinase,non-small cell lung cancer

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