{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T08:18:28Z","timestamp":1787818708315,"version":"build-2784847793"},"reference-count":26,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chronic Diseases and Translational Medicine"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors have transformed treatment strategies for metastatic non\u2010small cell lung cancer (mNSCLC). This study aimed to assess the efficacy and safety of durvalumab combined with tremelimumab compared with those of standard chemotherapy, particularly in patients with low or negative PD\u2010L1 expression, and in the overall population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic review and meta\u2010analysis of randomized controlled trials (RCTs) was conducted following PRISMA 2020 guidelines. Pooled efficacy and safety outcomes were calculated as hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three RCTs (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091859) were included. Durvalumab and tremelimumab significantly improved overall survival (OS) compared with that of chemotherapy (HR\u2009=\u20090.81, 95% CI: 0.67\u20130.99) in patients with PD\u2010L1\u2009&lt;\u20091%. Progression\u2010free survival (PFS) and objective response rate (ORR) were not significantly different in the overall population compared with those in the patient cohort. Treatment\u2010related adverse events (TRAEs) and grade \u2265\u20093 TRAEs were significantly lower in patients receiving the drug combination (RR\u2009=\u20090.78 and 0.64, respectively), whereas serious TRAEs were higher (RR\u2009=\u20091.41, 95% CI: 1.14\u20131.74) when compared with those receiving standard chemotherapy. No significant differences were observed in treatment\u2010related deaths.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Durvalumab plus tremelimumab may be a promising alternative to chemotherapy in patients with mNSCLC with low PD\u2010L1 expression for improving OS, although the PFS and ORR benefits were not significant in the overall population. This combination has a favorable safety profile, although it is associated with a higher risk of serious TRAEs. Further studies are required to confirm these findings.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>PROSPERO Protocol Registration:<\/jats:bold>\n                      CRD420250652760.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cdt3.70065","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T07:41:43Z","timestamp":1787816503000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and Safety of Durvalumab and Tremelimumab in Metastatic Non\u2010Small Cell Lung Cancer: A Systematic Review and Meta\u2010Analysis of Randomized Controlled Trials"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6872-8802","authenticated-orcid":false,"given":"Ikhwan","family":"Rinaldi","sequence":"first","affiliation":[{"name":"Division of Hematology and Medical Oncology, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine Universitas Indonesia Jakarta Indonesia"},{"name":"Gading Pluit Hospital, Boulevard Timur Raya, Kelapa Gading Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6672-6953","authenticated-orcid":false,"given":"Eric Ricardo","family":"Yonatan","sequence":"additional","affiliation":[{"name":"Gading Pluit Hospital, Boulevard Timur Raya, Kelapa Gading Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7346-1566","authenticated-orcid":false,"given":"Tasia","family":"Esterita","sequence":"additional","affiliation":[{"name":"Gading Pluit Hospital, Boulevard Timur Raya, Kelapa Gading Jakarta Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2021.4932"},{"issue":"4","key":"e_1_2_13_4_1","first-page":"291","article-title":"Non\u2010Small Cell Lung Carcinoma in Women: A Retrospective Cohort Study in Indonesia","volume":"50","author":"Sutandyo N.","year":"2018","journal-title":"Acta medica 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Approves Tremelimumab in Combination With Durvalumab and Platinum\u2010Based Chemotherapy for Metastatic Non\u2010Small Cell Lung Cancer","author":"Center for Drug Evaluation and Research","year":"2025"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.00975"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910231"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1302840"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1167975"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v7.i4.405"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2018.01.111"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines8040575"}],"container-title":["Chronic Diseases and Translational 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