{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T17:48:30Z","timestamp":1777312110734,"version":"3.51.4"},"reference-count":94,"publisher":"Hamad bin Khalifa University Press (HBKU Press)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024]]},"abstract":"<jats:p>Background: Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Despite advances in treatment options, the overall prognosis for advanced gastric cancer remains poor. Immunotherapy has revolutionized the field of cancer treatment by harnessing the patient\u2019s immune system to target and destroy cancer cells. Two important immune checkpoint inhibitors that have shown promise in various malignancies, including gastric cancer, are program death-1 and cytotoxic T lymphocyte-4 inhibitors.<\/jats:p>\n                  <jats:p>Aims: To assess and analyze the occurrence of adverse events associated with program death-1 and cytotoxic T lymphocyte antigen-4 in patients diagnosed with advanced gastric cancer.<\/jats:p>\n                  <jats:p>Methods: Relevant studies were searched in reputable databases such as PubMed, Embase, Google Scholar, and the Cochrane Library from October 6, 2017, to February 3, 2022. Studies were analyzed with Review Manager 5.4. PROSPERO: CRD42023479662.<\/jats:p>\n                  <jats:p>Results: Of the 500 studies retrieved, nine randomized control trials involving 5,185 patients were included in the meta-analysis comparing TRAEs in advanced gastric cancer patients after immune checkpoint inhibitor monotherapy and combined immune checkpoint inhibitors treatment. There was a lower risk of any grade of treatment-related adverse events with program death -1 than in the control arm (76.5% vs. 79%, P = 0.02). Program death-1 observed a lesser risk of grade 3-4 treatment-related adverse events as compared to the control for nausea (0.3% vs. 3%, P = 0.007) and fatigue (1% vs. 2.7%, P = 0.006). Program death-1 monotherapy also saw a decrease in the incidence of common treatment-related adverse events such as diarrhea (9.6% vs. 16%, P &lt; 0.00001), nausea (6.8% vs. 20.6%, P &lt; 0.00001) and fatigue (11% vs. 15.9%, P = 0.001). However, pruritus occurrence increased (3.8% vs. 9%, P &lt; 0.001) after program death-1 compared to control.<\/jats:p>\n                  <jats:p>Conclusions: Patients with advanced gastric cancer endured program death-1 treatment effectively. Nonetheless, the combination of program death-1 and cytotoxic T lymphocyte-4 results in a greater occurrence of treatment-related adverse events.<\/jats:p>","DOI":"10.5339\/qmj.2024.31","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T09:32:21Z","timestamp":1725442341000},"source":"Crossref","is-referenced-by-count":0,"title":["Exploring program death-1 and cytotoxic T lymphocyte antigen-4 safety in gastric cancer clinical trials: A meta-analysis"],"prefix":"10.5339","volume":"2024","author":[{"given":"Acquah","family":"Theophilus","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yahui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxin","family":"Da","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4924-3668","authenticated-orcid":true,"given":"Zhihong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, The Affiliated People\u2019s Hospital of Jiangsu University, Zhenjiang, China*Correspondence: Jie Ma jsdxmajie@163.com"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2318-5936","authenticated-orcid":true,"given":"Zakari","family":"Shaibu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China"},{"name":"Department of Gastrointestinal Surgery, The Affiliated People\u2019s Hospital of Jiangsu University, Zhenjiang, China*Correspondence: Jie Ma jsdxmajie@163.com"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3277","reference":[{"issue":"(1):","key":"CIT0001","series-title":"CA Cancer J Clin","first-page":"7-33","article-title":"Cancer Statistics, 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Eradication: A Nationwide Cancer Registry-Based Study in Taiwan","volume":"28","author":"Chang\n \nJS","year":"2019"},{"issue":"(1):","key":"CIT0006","series-title":"Prz Gastroenterol","first-page":"26-38","article-title":"Epidemiology of gastric cancer: global trends, risk factors and prevention","volume":"14","author":"Rawla\n \nP","year":"2019;"},{"issue":"(2):","key":"CIT0007","series-title":"J Pathol Transl Med","first-page":"103-121","article-title":"Molecular Testing for Gastrointestinal Cancer","volume":"51","author":"Lee\n \nHS","year":"2017"},{"issue":"(1):","key":"CIT0008","series-title":"N Engl J Med","first-page":"11-20","article-title":"Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer","volume":"355","author":"Cunningham\n \nD","year":"2006"},{"issue":"(9742):","key":"CIT0009","series-title":"Lancet","first-page":"687-97","article-title":"Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of 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(COVID-19): Causative agent, mental health concerns, and potential management options","volume":"13","author":"Khan\n \nS","year":"2020"},{"issue":"(9):","key":"CIT0014","series-title":"Int J Biol Sci","first-page":"1816-1834","article-title":"Impact of chronically alternating light-dark cycles on circadian clock mediated expression of cancer (glioma)-related genes in the brain","volume":"15","author":"Khan\n \nS","year":"2019"},{"issue":"(4):","key":"CIT0015","series-title":"Nat Rev Cancer","first-page":"252-64","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll\n \nDM","year":"2012"},{"issue":"(8):","key":"CIT0016","series-title":"Blood","first-page":"1537-44","article-title":"Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired","volume":"114","author":"Ahmadzadeh\n \nM","year":"2009"},{"issue":"(11):","key":"CIT0017","series-title":"Nat 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and Efficacy of Re-treating with Immunotherapy after Immune-Related Adverse Events in Patients with NSCLC","volume":"6","author":"Santini\n \nFC","year":"2018"},{"issue":"(11):","key":"CIT0026","series-title":"Immunotherapy","first-page":"1213-27","article-title":"Risk of gastrointestinal complications in cancer patients treated with immune checkpoint inhibitors: a meta-analysis","volume":"7","author":"Abdel-Rahman\n \nO","year":"2015;"},{"key":"CIT0027","series-title":"BMJ","first-page":"n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page\n \nMJ","year":"2021"},{"key":"CIT0028","article-title":"Users\u2019 Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice, 3E: McGraw-Hill Education \/ Medical;","author":"G\n \nG","year":"2014"},{"issue":"(7):","key":"CIT0029","series-title":"PLoS Med","first-page":"e1000097","article-title":"Preferred reporting items for systematic reviews 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Oncol","first-page":"966-977","article-title":"Phase III Trial of Avelumab Maintenance After First-Line Induction Chemotherapy Versus Continuation of Chemotherapy in Patients With Gastric Cancers: Results From JAVELIN Gastric 100","volume":"39","author":"Moehler\n \nM","year":"2021"},{"key":"CIT0040","series-title":"Common Terminology Criteria for Adverse Events, version 4.0. 2009","article-title":"National Cancer Institute","year":"2014"},{"issue":"(47):","key":"CIT0041","series-title":"Medicine (Baltimore)","first-page":"e18054","article-title":"Efficacy and safety of anti-PD-1\/PD-L1 agents vs chemotherapy in patients with gastric or gastroesophageal junction cancer: a systematic review and meta-analysis","volume":"98","author":"Wang\n \nBC","year":"2019"},{"issue":"(5):","key":"CIT0042","series-title":"Oncoimmunology","first-page":"e1581547","article-title":"Efficacy and safety of immune checkpoint inhibitors in advanced gastric or gastroesophageal junction cancer: a systematic 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Review","author":"Shaibu\n \nZ ZW","year":"2022;"},{"issue":"(12):","key":"CIT0044","series-title":"Expert Rev Anticancer Ther","first-page":"1231-1239","article-title":"Health-related quality of life in cancer patients treated with PD-(L)1 inhibitors: a systematic review","volume":"18","author":"Abdel-Rahman\n \nO","year":"2018"},{"issue":"(10272):","key":"CIT0045","series-title":"Lancet","first-page":"375-386","article-title":"First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial","volume":"397","author":"Baas\n \nP","year":"2021"},{"issue":"(4):","key":"CIT0046","series-title":"Ann Transl Med","first-page":"290","article-title":"Efficacy and safety of immune checkpoint inhibitors in gastric cancer: a network meta-analysis of well-designed randomized controlled trials","volume":"9","author":"Pan\n \nS","year":"2021"},{"issue":"(48):","key":"CIT0047","series-title":"Medicine (Baltimore)","first-page":"e8931","article-title":"Risk of gastrointestinal toxicities with PD-1 inhibitors in cancer patients: A meta-analysis of randomized clinical trials","volume":"96","author":"Wei\n \nW","year":"2017"},{"issue":"(1):","key":"CIT0001","series-title":"CA Cancer J Clin","first-page":"7-33","article-title":"Cancer Statistics, 2021","volume":"71","author":"Siegel\n \nRL","year":"2021"},{"issue":"(3):","key":"CIT0002","series-title":"CA Cancer J Clin","first-page":"209-249","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung\n \nH","year":"2021"},{"issue":"(1):","key":"CIT0003","series-title":"J Gastric Cancer","first-page":"207-223","article-title":"Recent Progress in Immunotherapy for Gastric Cancer","volume":"23","author":"Yoon\n \nJ","year":"2023"},{"issue":"Suppl 6:","key":"CIT0004","series-title":"Ann Oncol","first-page":"vi57-63","article-title":"Gastric cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"24","author":"Waddell\n \nT","year":"2013"},{"issue":"(10):","key":"CIT0005","series-title":"Cancer Epidemiol Biomarkers Prev","first-page":"1694-1703","article-title":"The Epidemiology of Gastric Cancers in the Era of Helicobacter pylori Eradication: A Nationwide Cancer Registry-Based Study in Taiwan","volume":"28","author":"Chang\n \nJS","year":"2019"},{"issue":"(1):","key":"CIT0006","series-title":"Prz Gastroenterol","first-page":"26-38","article-title":"Epidemiology of gastric cancer: global trends, risk factors and prevention","volume":"14","author":"Rawla\n \nP","year":"2019;"},{"issue":"(2):","key":"CIT0007","series-title":"J Pathol Transl Med","first-page":"103-121","article-title":"Molecular Testing for Gastrointestinal Cancer","volume":"51","author":"Lee\n \nHS","year":"2017"},{"issue":"(1):","key":"CIT0008","series-title":"N Engl J Med","first-page":"11-20","article-title":"Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer","volume":"355","author":"Cunningham\n \nD","year":"2006"},{"issue":"(9742):","key":"CIT0009","series-title":"Lancet","first-page":"687-97","article-title":"Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial","volume":"376","author":"Bang\n \nYJ","year":"2010"},{"key":"CIT0010","series-title":"Front Immunol","first-page":"948647","article-title":"Recent Progress and Future Perspectives of Immunotherapy in Advanced Gastric Cancer","volume":"13","author":"Jin\n \nX","year":"2022"},{"issue":"(6):","key":"CIT0011","series-title":"Expert Rev Clin Pharmacol","first-page":"609-619","article-title":"Immunotherapy for gastric 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