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      Absolute Neutrophil Count in the Peripheral Blood Predicts Prognosis in Lung Cancer Patients Treated with Anlotinib

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          Abstract

          Purpose

          Anlotinib is a multi-targeted tyrosine kinase inhibitor that inhibits tumor angiogenesis and cell proliferation. It is widely used as a third-line therapy for lung cancer. However, reliable prognostic biomarkers for predicting the efficacy of anlotinib are lacking. We conducted a retrospective study to investigate the prognostic value of serological inflammatory biomarkers in anlotinib treatment.

          Patients and Methods

          Patients with advanced lung cancer treated with anlotinib monotherapy were enrolled. Cox regression was conducted to analyze the significant factors related to progression-free survival (PFS) and overall survival (OS). The objective response rate (ORR) was compared based on the median cut-off value of the significant inflammation index. Meanwhile, we created survival curves to compare the two groups and performed receiver operating characteristic curve analysis to assess the predictive ability of the inflammation index.

          Results

          Among a total of 71 patients, the median PFS was 5.5 months and the median OS was 9.5 months. The ORR and disease control rate were 16.9% and 84.5%, respectively. According to univariate and multivariate analyses, absolute neutrophil count (ANC) was the only indicator associated with both PFS (hazard ratio [HR] =1.095, 95% confidence interval [CI] 1.030–1.163, P=0.003) and OS (HR=1.057, 95% CI 1.003–1.113, P=0.037). In the group with ANC ≥4.58, the ORR was relatively lower (8.1% vs 26.5%, P=0.057), but not statistically significant; PFS and OS were relatively shorter (median PFS 5.0 [95% CI 4.4–9.6] vs 7.0 months [95% CI 4.4–5.7], P=0.024 and median OS 7.3 [95% CI 4.7–10.0] vs 17.6 months [95% CI 12.3–22.9], P < 0.001). ANC had a relatively high discriminatory ability to predict 10-month survival, with an area under the curve of 0.729, sensitivity of 82.5%, and specificity of 67.7%.

          Conclusion

          Elevated pre-treatment ANC was associated with a poor prognosis. Patients with lower peripheral blood levels of ANC might benefit from anlotinib.

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          Most cited references29

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non–Small Cell Lung Cancer

            Anlotinib is a novel multitarget tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling. A phase 2 trial showed anlotinib to improve progression-free survival with a potential benefit of overall survival, leading to the phase 3 trial to confirm the drug's efficacy in advanced non-small cell lung cancer (NSCLC).
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              Anlotinib: a novel multi-targeting tyrosine kinase inhibitor in clinical development

              Anlotinib is a new, orally administered tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit. Compared to the effect of placebo, it improved both progression-free survival (PFS) and overall survival (OS) in a phase III trial in patients with advanced non-small-cell lung cancer (NSCLC), despite progression of the cancer after two lines of prior treatments. Recently, the China Food and Drug Administration (CFDA) approved single agent anlotinib as a third-line treatment for patients with advanced NSCLC. Moreover, a randomized phase IIB trial demonstrated that anlotinib significantly prolonged the median PFS in patients with advanced soft tissue sarcoma (STS). Anlotinib also showed promising efficacy in patients with advanced medullary thyroid carcinoma and metastatic renal cell carcinoma (mRCC). The tolerability profile of anlotinib is similar to that of other tyrosine kinase inhibitors that target VEGFR and other tyrosine kinase-mediated pathways; however, anlotinib has a significantly lower incidence of grade 3 or higher side effects compared to that of sunitinib. We review the rationale, clinical evidence, and future perspectives of anlotinib for the treatment of multiple cancers.
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                Author and article information

                Journal
                Cancer Manag Res
                Cancer Manag Res
                cmar
                cancmanres
                Cancer Management and Research
                Dove
                1179-1322
                03 May 2021
                2021
                : 13
                : 3619-3627
                Affiliations
                [1 ]Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , Shanghai, People’s Republic of China
                [2 ]Institute of Respiratory Diseases, Shanghai Jiao Tong University School of Medicine , Shanghai, People’s Republic of China
                Author notes
                Correspondence: Yi Guo; Ranran Dai Department of Respiratory and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine , No. 197, Rui Jin 2nd Road, Shanghai, 200025, People’s Republic of ChinaTel +86 131 6622 1556; Tel +86 131 6622 1556Fax +86 21 6467 4301 Email guoyi621@qq.com; drr11154@rjh.com.cn
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-5233-9693
                Article
                307368
                10.2147/CMAR.S307368
                8106457
                33976572
                a86f47ef-4a3b-45fd-a1af-bb8aca122f35
                © 2021 Chen et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 19 February 2021
                : 01 April 2021
                Page count
                Figures: 4, Tables: 10, References: 29, Pages: 9
                Funding
                Funded by: National Key R&D Program of China;
                Funded by: National Natural Science Foundation of China, open-funder-registry 10.13039/501100001809;
                Funded by: ant of Beijing Bethune Charitable Foundation;
                Funded by: Shanghai Key Discipline for Respiratory Diseases;
                This work was supported by National Key R&D Program of China [granted number 2017YFC1309701, 2017YFC1309700 and 2018YFC1311900]; National Natural Science Foundation of China [granted number 81570029]; Grant of Beijing Bethune Charitable Foundation [granted number BJ-RW2020003J] and Shanghai Key Discipline for Respiratory Diseases [granted number 2017ZZ02014].
                Categories
                Original Research

                Oncology & Radiotherapy
                lung cancer,anlotinib,absolute neutrophil count,progression-free survival,overall survival

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