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PubMed, EMBASE, and the Cochrane Library databases were systematically searched without language restrictions from inception to May 31, 2024 to identify Phase 3 randomized controlled trials of lung cancer comparing PD\u20101\/PD\u2010L1 inhibitors versus placebo\/best supportive care (alone or in combination with nontargeted chemotherapy) that had available data regarding treatment\u2010related adverse events (TRAEs) or incidence and sample size. Random\u2010effect models were employed to study the pooled relative risk (RR) and 95% confidence intervals (CIs). Finally, 36 trials, involving 19,693 participants, fulfilled the inclusion criteria. PD\u20101\/PD\u2010L1 inhibitors significantly augmented the likelihood of developing all\u2010grade (RR, 1.03; 95% CI, 1.01\u20131.04,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.01) and grade\u2009\u22653 TRAEs (RR, 1.16; 95% CI, 1.10 to 1.23,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.01). PD\u20101\/PD\u2010L1 inhibitors substantially augmented the odds of developing treatment\u2010related serious adverse events (SAEs) (RR, 1.48; 95% CI, 1.27\u20131.71,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.01) and fatal adverse events (FAEs) (RR, 1.42; 95% CI, 1.11\u20131.82,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u2009.01). Subgroup analyses indicated that the RR of SAEs and FAEs were generally consistent, regardless of treatment type, tumor type, treatment setting, PD\u20101\/PD\u2010L1 inhibitors type and study design. The most common causes of FAEs were respiratory failure\/insufficiency (33.3%), cardiac events (16.1%), and hematological disorders (10.1%). We demonstrated that PD\u20101\/PD\u2010L1 inhibitors were significantly correlated with higher possibility of developing treatment\u2010related toxicities, especially SAEs and FAEs, compared with placebo\/best supportive care controls.\n                  <\/jats:p>","DOI":"10.1002\/ijc.35195","type":"journal-article","created":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T11:13:10Z","timestamp":1727262790000},"page":"608-622","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The risk of treatment\u2010related toxicities with\n                    <scp>PD<\/scp>\n                    \u20101\/\n                    <scp>PD<\/scp>\n                    \u2010\n                    <scp>L1<\/scp>\n                    inhibitors in patients with lung cancer"],"prefix":"10.1002","volume":"156","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4987-7618","authenticated-orcid":false,"given":"Hao","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Radiation Therapy General Hospital of Southern Theater Command  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Changde Hospital, Xiangya School of Medicine Central South University (The First People's Hospital of Changde City)  Changde China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6237-0811","authenticated-orcid":false,"given":"Si\u2010Cai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiation Therapy General Hospital of Southern Theater Command  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Ze","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Radiation Therapy General Hospital of Southern Theater Command  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiation Therapy General Hospital of Southern Theater Command  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Yong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Radiation Therapy General Hospital of Southern 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