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      The optimal timing and courses of bevacizumab added to chemotherapy for non-squamous non-small cell lung cancer: revelations from the real-world experience in a single Chinese cancer center

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          Abstract

          Background

          Bevacizumab combined with platinum-based chemotherapy has been approved in the first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC) without driver genes, but this regimen for second-line or later-line treatment of non-squamous NSCLC remains to be further tested. Our study aimed to provide data on the safety and effectiveness of bevacizumab (Bev)-containing chemotherapy in different-line settings for patients with NSCLC in the Chinese real-world clinical routine practice and to explore predictors for progression-free survival (PFS) and overall survival (OS).

          Methods

          We reviewed the medical records of 194 patients with non-squamous NSCLC who received Bev plus chemotherapy as the first-, second- or third- or later-line treatment between December 2009 and January 2020 at Fudan University, Shanghai Cancer Center. Clinical characteristics, treatment history, clinical evaluation, and adverse effects of each patient were deeply analyzed. PFS and OS were estimated by the Kaplan-Meier method. Univariate and multivariate analyses were conducted to find predictors of longer PFS and OS.

          Results

          One hundred ninety-four patients were enrolled in this study, including 102 (52.6%), 58 (29.9%) and 34 (17.5%) patients received Bev in combination with the first-line chemotherapy (Bev + Che1), second-line chemotherapy (Bev + Che2) and third-/later-line chemotherapy (Bev + Che3), respectively. Administration of Bev in combination with the first-line chemotherapy and >6 courses were independent predictors of significantly prolonged PFS. Whereas, patients older than 65 years or with ECOG PS ≥2 may not benefit more from Bev added to the first-line chemotherapy compared to second-/later-line chemotherapy. PFS of patients received treatment with/without chemotherapy as maintenance therapy showed no significant difference (P=0.354) in >6 courses Bev cohort. As for OS, Bev plus the first-line chemotherapy and number of metastatic sites <3 were independent predictors. The most common adverse effects (AE) were leukopenia, neutropenia, hypertension, and proteinuria. Twenty patients suffered from AE ≥ Grade 3.

          Conclusions

          Bev, in combination with the front-line chemotherapy, is proven beneficial for survival well-tolerated.

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          Most cited references19

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          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer

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              Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial.

              Despite recent advances in the treatment of advanced non-small-cell lung cancer, there remains a need for effective treatments for progressive disease. We assessed the efficacy of pembrolizumab for patients with previously treated, PD-L1-positive, advanced non-small-cell lung cancer.
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                Author and article information

                Journal
                Ann Transl Med
                Ann Transl Med
                ATM
                Annals of Translational Medicine
                AME Publishing Company
                2305-5839
                2305-5847
                October 2020
                October 2020
                : 8
                : 20
                : 1311
                Affiliations
                [1 ]Department of Medical Oncology, Fudan University Shanghai Cancer Center , Shanghai, China;
                [2 ]Department of Oncology, Shanghai Medical College, Fudan University , Shanghai, China;
                [3 ]Institute of Thoracic Oncology, Fudan University , Shanghai, China
                Author notes

                Contributions: (I) Conception and design: J Wang, X Zhao; (II) Administrative support: X Wu, H Wang, H Yu; (III) Provision of study materials or patients: Y Feng, C Liu, Q Long; (IV) Collection and assembly of data: Q Long, Y Feng, C Liu, X Zhao, J Wang; (V) Data analysis and interpretation: Q Long, Y Feng, C Liu, X Zhao, J Wang; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                [#]

                These authors contributed equally to this work.

                Correspondence to: Xinmin Zhao; Jialei Wang. Department of Medical Oncology, Fudan University Shanghai Cancer Center, No. 270 Dong An Road, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, No. 138 Yi Xue Yuan Road, Shanghai, China. Email: mizuyiaaa@ 123456163.com ; m18017312369@ 123456163.com .
                Article
                atm-08-20-1311
                10.21037/atm-20-6327
                7661884
                33209891
                46c4fa49-3f45-4fa9-9a40-d1a0a57b1bdd
                2020 Annals of Translational Medicine. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 13 August 2020
                : 13 October 2020
                Categories
                Original Article

                non-small cell lung cancer (nsclc),bevacizumab (bev),chemotherapy,predictor

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