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      Efficacy and safety of anti-epidermal growth factor receptor agents for the treatment of oesophageal cancer: a systematic review and meta-analysis

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          Abstract

          Objectives

          Despite remarkable advances in the treatment of oesophageal cancer (OC), the role of antiepidermal growth factor receptor (anti-EGFR) agents in treating OC remains controversial. Herein, a systematic review and meta-analysis were conducted to elucidate the efficacy and safety of anti-EGFR agents in patients with OC.

          Design

          Meta-analysis of randomised controlled trials (RCTs) identified by searching the PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane Library, Chinese Biology Medicine, China National Knowledge Infrastructure and Wanfang Data Knowledge Service Platform databases from inception to December 2019. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

          Setting

          RCTs from any country and healthcare setting.

          Participants

          Patients with OC.

          Interventions

          Combination therapy with anti-EGFR agents and conventional treatments versus conventional treatments alone in patients with OC.

          Primary and secondary outcome measures

          Overall survival (OS) and progression-free survival (PFS) were primary outcome measures, and objective response rate (ORR), disease control rate (DCR) and treatment toxicities were secondary outcome measures.

          Results

          In total, 25 RCTs comprising 3406 patients with OC were included. Overall, anti-EGFR treatment significantly improved the OS (HR: 0.81, 95% CI 0.74 to 0.89, p<0.00001), ORR (relative risk (RR): 1.33, 95% CI 1.16 to 1.52, p<0.0001) and DCR (RR: 1.22, 95% CI 1.11 to 1.34, p<0.0001) but not PFS (HR: 0.91, 95% CI 0.76 to 1.08, p=0.26). Anti-EGFR treatment was significantly associated with higher incidences of myelosuppression, diarrhoea, acne-like rash and hypomagnesaemia.

          Conclusions

          Overall, anti-EGFR agents have positive effects on OS, the ORR and DCR in OC. However, considering the high incidence of adverse effects, such as myelosuppression, diarrhoea, acne-like rashes and hypomagnesaemia, careful monitoring of patients with OC is recommended during anti-EGFR treatment.

          Trial registration number

          CRD42020169230.

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          Most cited references66

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)
          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

            David Moher, Alessandro Liberati, Jennifer Tetzlaff … (2012)
            David Moher and colleagues introduce PRISMA, an update of the QUOROM guidelines for reporting systematic reviews and meta-analyses
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              Cancer statistics in China, 2015.

              Wanqing Chen, Rongshou Zheng, Peter D Baade … (2016)
              With increasing incidence and mortality, cancer is the leading cause of death in China and is a major public health problem. Because of China's massive population (1.37 billion), previous national incidence and mortality estimates have been limited to small samples of the population using data from the 1990s or based on a specific year. With high-quality data from an additional number of population-based registries now available through the National Central Cancer Registry of China, the authors analyzed data from 72 local, population-based cancer registries (2009-2011), representing 6.5% of the population, to estimate the number of new cases and cancer deaths for 2015. Data from 22 registries were used for trend analyses (2000-2011). The results indicated that an estimated 4292,000 new cancer cases and 2814,000 cancer deaths would occur in China in 2015, with lung cancer being the most common incident cancer and the leading cause of cancer death. Stomach, esophageal, and liver cancers were also commonly diagnosed and were identified as leading causes of cancer death. Residents of rural areas had significantly higher age-standardized (Segi population) incidence and mortality rates for all cancers combined than urban residents (213.6 per 100,000 vs 191.5 per 100,000 for incidence; 149.0 per 100,000 vs 109.5 per 100,000 for mortality, respectively). For all cancers combined, the incidence rates were stable during 2000 through 2011 for males (+0.2% per year; P = .1), whereas they increased significantly (+2.2% per year; P < .05) among females. In contrast, the mortality rates since 2006 have decreased significantly for both males (-1.4% per year; P < .05) and females (-1.1% per year; P < .05). Many of the estimated cancer cases and deaths can be prevented through reducing the prevalence of risk factors, while increasing the effectiveness of clinical care delivery, particularly for those living in rural areas and in disadvantaged populations.
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                Author and article information

                Journal
                Journal ID (nlm-ta): BMJ Open
                Journal ID (iso-abbrev): BMJ Open
                Journal ID (hwp): bmjopen
                Journal ID (publisher-id): bmjopen
                Title: BMJ Open
                Publisher: BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                ISSN (Electronic): 2044-6055
                Publication date Collection: 2021
                Publication date (Electronic): 22 March 2021
                Volume: 11
                Issue: 3
                Electronic Location Identifier: e046352
                Affiliations
                [1 ]departmentSchool of Nursing , Liaoning University of Traditional Chinese Medicine , Shenyang, China
                [2 ]departmentSchool of Nursing , Tianjin Medical University , Tianjin, China
                [3 ]departmentDepartment of Colorectal Surgery , Liaoning Cancer Institute and Hospital , Shenyang, China
                [4 ]departmentDepartment of Critical Care Medicine , Liaoning Cancer Institute and Hospital , Shenyang, China
                [5 ]departmentDepartment of Science and Technology , Liaoning University of Traditional Chinese Medicine , Shenyang, China
                Author notes
                [Correspondence to ] Dr Rui Yu; yurui1969@ 123456163.com
                Author information
                http://orcid.org/0000-0002-4506-5081
                Article
                Publisher ID: bmjopen-2020-046352
                DOI: 10.1136/bmjopen-2020-046352
                PMC ID: 7986677
                PubMed ID: 33753446
                SO-VID: 01f1eb23-3f90-4f10-a36a-03d4f5018182
                Copyright © © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
                License:

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:  http://creativecommons.org/licenses/by-nc/4.0/.

                History
                Date received : 28 October 2020
                Date revision received : 25 February 2021
                Date accepted : 03 March 2021
                Funding
                Funded by: Liaoning Social Science Planning Fund Project;
                Award ID: L19CSH002
                Categories
                Subject: Oncology
                Subject: 1506
                Subject: 1717
                Series title: Original research
                Custom metadata
                special-feature unlocked

                ScienceOpen disciplines: Medicine
                Keywords: oncology,therapeutics,oesophageal disease
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: oncology, therapeutics, oesophageal disease

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