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      Advances in Targeted Therapy and Immunotherapy for Non-small Cell Lung Cancer Based on Accurate Molecular Typing

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          Abstract

          The essence of precision medicine is to achieve the goal of “individualized treatment” through genotyping of patients and targeted therapy. At present, the pathogenic genes of non-small cell lung cancer (NSCLC) have been studied most thoroughly and targeted therapy based on genotyping has been the most successful. This paper focuses on the precision treatment of NSCLC based on genotyping, comparing gene detection methods and summarize the latest progress of NSCLC immunotherapy.

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          Most cited references39

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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

          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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            Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial.

            More persons in the United States die from non-small cell lung cancer (NSCLC) than from breast, colorectal, and prostate cancer combined. In preclinical testing, oral gefitinib inhibited the growth of NSCLC tumors that express the epidermal growth factor receptor (EGFR), a mediator of cell signaling, and phase 1 trials have demonstrated that a fraction of patients with NSCLC progressing after chemotherapy experience both a decrease in lung cancer symptoms and radiographic tumor shrinkages with gefitinib. To assess differences in symptomatic and radiographic response among patients with NSCLC receiving 250-mg and 500-mg daily doses of gefitinib. Double-blind, randomized phase 2 trial conducted from November 2000 to April 2001 in 30 US academic and community oncology centers. Patients (N = 221) had either stage IIIB or IV NSCLC for which they had received at least 2 chemotherapy regimens. Daily oral gefitinib, either 500 mg (administered as two 250-mg gefitinib tablets) or 250 mg (administered as one 250-mg gefitinib tablet and 1 matching placebo). Improvement of NSCLC symptoms (2-point or greater increase in score on the summed lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [FACT-L] instrument) and tumor regression (>50% decrease in lesion size on imaging studies). Of 221 patients enrolled, 216 received gefitinib as randomized. Symptoms of NSCLC improved in 43% (95% confidence interval [CI], 33%-53%) of patients receiving 250 mg of gefitinib and in 35% (95% CI, 26%-45%) of patients receiving 500 mg. These benefits were observed within 3 weeks in 75% of patients. Partial radiographic responses occurred in 12% (95% CI, 6%-20%) of individuals receiving 250 mg of gefitinib and in 9% (95% CI, 4%-16%) of those receiving 500 mg. Symptoms improved in 96% of patients with partial radiographic responses. The overall survival at 1 year was 25%. There were no significant differences between the 250-mg and 500-mg doses in rates of symptom improvement (P =.26), radiographic tumor regression (P =.51), and projected 1-year survival (P =.54). The 500-mg dose was associated more frequently with transient acne-like rash (P =.04) and diarrhea (P =.006). Gefitinib, a well-tolerated oral EGFR-tyrosine kinase inhibitor, improved disease-related symptoms and induced radiographic tumor regressions in patients with NSCLC persisting after chemotherapy.
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              Brigatinib versus Crizotinib in ALK-Positive Non–Small-Cell Lung Cancer

              Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, has robust efficacy in patients with ALK-positive non-small-cell lung cancer (NSCLC) that is refractory to crizotinib. The efficacy of brigatinib, as compared with crizotinib, in patients with advanced ALK-positive NSCLC who have not previously received an ALK inhibitor is unclear.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                12 March 2019
                2019
                : 10
                : 230
                Affiliations
                [1] 1Lung Cancer Center of West China Hospital, Sichuan University , Chengdu, China
                [2] 2The Medical Department, 3D Medicines Inc. , Shanghai, China
                Author notes

                Edited by: Shuang Zhou, University of Houston, United States

                Reviewed by: Pooja Dhupkar, University of Texas MD Anderson Cancer Center, United States; Lu Zhao, Zhejiang University, China

                *Correspondence: Qinghua Zhou, zhouqh135@ 123456163.com

                This article was submitted to Pharmaceutical Medicine and Outcomes Research, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2019.00230
                6424010
                30930778
                323fc0ea-e5b2-45b3-b3ac-21af1c98ff49
                Copyright © 2019 Dong, Li, Lin, Zhou and Huang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 December 2018
                : 22 February 2019
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 81, Pages: 10, Words: 0
                Funding
                Funded by: Department of Science and Technology of Sichuan Province 10.13039/501100004829
                Award ID: 2018SZ0152
                Funded by: Health and Family Planning Commission of Sichuan Province 10.13039/501100009564
                Award ID: 18PJ432
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                nsclc,targeted therapy,immunotherapy,egfr,pd-l1,alk,ros1
                Pharmacology & Pharmaceutical medicine
                nsclc, targeted therapy, immunotherapy, egfr, pd-l1, alk, ros1

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