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      Predictors of Outcomes in Patients with EGFR-Mutated Non-Small Cell Lung Cancer Receiving EGFR Tyrosine Kinase Inhibitors: A Systematic Review and Meta-Analysis

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          Abstract

          Some commonly available patient or disease characteristics may be associated with progression-free survival (PFS) and overall survival (OS) in EGFR-mutant non-small cell lung cancer (NSCLC) patients receiving EGFR-TKIs (epidermal growth factor receptor - tyrosine kinase inhibitors). We performed a systematic review and meta-analysis of randomized control trials (RCTs) to explore differences in outcomes associated with EGFR-TKIs among subgroups of EGFR-mutant NSCLC patients. Pooled HRs for progression or death (PFS-HRs) and pooled HRs for death (OS-HRs) were compared among sub-groups defined according to baseline clinical and demographic variables as well as type of EGFR mutation. In the entire assessable population of 4465 EGFR-mutant NSCLC patients, significant interactions with PFS were found for gender (males vs. females; pooled ratio of the PFS-HRs = 1.2; 95% CI 1.12–1.56), smoking history (smokers vs. non-smokers; pooled ratio of the PFS-HRs = 1.26; 95% CI 1.05–1.51), and type of EGFR mutation (patients with exon 21 L858R mutation vs. exon 19 deletion; pooled ratio of the PFS-HRs = 1.39; 95% CI 1.18–1.63). Male patients, smokers and patients with EGFR exon 21 L858R mutation may derive less benefit from EGFR-TKIs compared to female patients, non-smokers and patients with EGFR exon 19 deletion.

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          Most cited references20

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          Cancer immunotherapy efficacy and patients' sex: a systematic review and meta-analysis

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            First-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance therapy for patients with advanced EGFR mutation-positive lung adenocarcinoma (CONVINCE): a phase 3, open-label, randomized study.

            Icotinib has been previously shown to be non-inferior to gefitinib in non-selected advanced non-small-cell lung cancer patients when given as second- or further-line treatment. In this open-label, randomized, phase 3 CONVINCE trial, we assessed the efficacy and safety of first-line icotinib versus cisplatin/pemetrexed plus pemetrexed maintenance in lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) mutation.
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              Gefitinib or Erlotinib vs Chemotherapy for EGFR Mutation-Positive Lung Cancer: Individual Patient Data Meta-Analysis of Overall Survival.

              We performed an individual patient data meta-analysis to examine the impact of first-generation epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor (TKI) therapy on overall survival (OS) in advanced non-small cell lung cancer (NSCLC).
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                28 August 2019
                September 2019
                : 11
                : 9
                : 1259
                Affiliations
                [1 ]Regional Reference Center for Rare Tumors, Department of Oncology and Hematology, AOU Federico II of Naples, 80131 Naples, Italy
                [2 ]National Reference Center for Environmental Health, Zoo-prophylactic Institute of Southern Italy, 80055 Portici, Italy
                [3 ]Department of Clinical Medicine and Surgery, University Federico II of Naples, Via Pansini 5, 80131 Naples, Italy
                [4 ]Department of Public Health, Federico II University of Naples, 80131 Naples, Italy
                [5 ]Department of Medicine and Health Sciences ‘Vincenzo Tiberio’, University of Molise, 86100 Campobasso, Italy
                Author notes
                Author information
                https://orcid.org/0000-0002-7588-6067
                https://orcid.org/0000-0001-8114-2577
                https://orcid.org/0000-0001-7205-5105
                Article
                cancers-11-01259
                10.3390/cancers11091259
                6770537
                31466227
                8464e67f-76e5-42b1-91f8-ae97606b516e
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 27 July 2019
                : 20 August 2019
                Categories
                Review

                non-small cell lung cancer,epidermal growth factor receptor tyrosine kinase inhibitors,sex

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