PMID- 35812997 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2589-5370 (Electronic) IS - 2589-5370 (Linking) VI - 50 DP - 2022 Aug TI - Toxicity spectrum of immunotherapy in advanced lung cancer: A safety analysis from clinical trials and a pharmacovigilance system. PG - 101535 LID - 10.1016/j.eclinm.2022.101535 [doi] LID - 101535 AB - BACKGROUND: With the increased use of immune checkpoint inhibitors (ICIs) in advanced lung cancer, adverse events (AEs), particularly immune-related AEs (irAEs), have garnered considerable interest. We conducted a comprehensive assessment of the toxicity profile in advanced lung cancer using multi-source medical data. METHODS: First, we systematically searched the PubMed, Embase, and Cochrane Library databases (from inception to 10 August 2021) for relevant randomised controlled trials (RCTs) involving ICI-based treatments for advanced lung cancer. The primary outcomes were treatment-related AEs and irAEs, including events that were assigned grade 1-5 and 3-5. The secondary outcomes were grade 5 AEs and irAEs (grade 1-5 and grade 3-5) in specific organs. Network comparisons were conducted for 11 treatments, including chemotherapy (CT), ICI monotherapy (three regimens: programmed death-1 receptor [PD-1] inhibitors, programmed death ligand-1 [PD-L1] inhibitors, and cytotoxic T lymphocyte-associated antigen [CTLA-4] inhibitors), dual-ICI combination therapy (two regimens), and treatment using one or two ICI drugs administered in combination with CT (five regimens). We also conducted a disproportionality analysis by extracting reports of various irAEs associated with ICIs from the FDA Adverse Event Reporting System (FAERS) database. The reporting odds ratios and fatality proportions of different irAEs were calculated and compared. PROSPERO: CRD42021268650. FINDINGS: Overall, 41 RCTs involving 23,121 patients with advanced lung cancer were included. Treatments containing chemotherapy increased the risk of treatment-related AEs compared to ICI-based regimens without chemotherapy. Concerning irAEs, PD-L1 + CTLA-4 + CT was associated with the highest risk of grade 1-5 irAEs, followed by two regimens of dual ICI combination, three regimens of ICI monotherapy, and three regimens of one ICI combined with CT. For 3-5 irAEs, CTLA-4 accounted for most AEs. Detailed comparisons of ICI-based treatment options provided irAE profiles based on specific organs/systems and AE severity. Insights from the FAERS database revealed that signals corresponding to pneumonitis, colitis, thyroiditis, and hypophysitis were observed across all ICI regimens. Further analyses of the outcomes indicated that myocarditis (163 of 367, 44.4%), pneumonitis (1610 of 4497, 35.8%), and hepatitis (290 of 931, 31.1%) had high fatality rates. INTERPRETATION: Included RCTs showed heterogeneity in a few clinical factors, and reports derived from the FAERS database might have involved inaccurate data. Our results can be used as a basis for improving clinical treatment strategies and designing preventive methods for ICI treatment in advanced lung cancer. FUNDING: This study was supported by the Research Project of Drug Clinical Comprehensive Evaluation and Drug Treatment Pathway (SHYXH-ZP-2021-001, SHYXH-ZP-2021-006), Clinical Research Innovation and Cultivation Fund of Ren Ji Hospital (RJPY-LX-008), Ren Ji Boost Project of National Natural Science Foundation of China (RJTJ-JX-001), and Shanghai "Rising Stars of Medical Talent" Youth Development Program - Youth Medical Talents - Clinical Pharmacist Program (SHWJRS (2019) 072). CI - (c) 2022 The Author(s). FAU - Yan, Yi-Dan AU - Yan YD AD - Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. AD - Drug Clinical Comprehensive Evaluation Group, Shanghai Pharmaceutical Association, Shanghai 200040, China. FAU - Zhao, Ying AU - Zhao Y AD - Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. FAU - Zhang, Chi AU - Zhang C AD - Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. AD - Drug Clinical Comprehensive Evaluation Group, Shanghai Pharmaceutical Association, Shanghai 200040, China. FAU - Fu, Jie AU - Fu J AD - Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. FAU - Su, Ying-Jie AU - Su YJ AD - Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. AD - Drug Clinical Comprehensive Evaluation Group, Shanghai Pharmaceutical Association, Shanghai 200040, China. FAU - Cui, Xiang-Li AU - Cui XL AD - Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China. FAU - Ma, Er-Li AU - Ma EL AD - Drug Clinical Comprehensive Evaluation Group, Shanghai Pharmaceutical Association, Shanghai 200040, China. FAU - Liu, Bing-Long AU - Liu BL AD - Drug Clinical Comprehensive Evaluation Group, Shanghai Pharmaceutical Association, Shanghai 200040, China. FAU - Gu, Zhi-Chun AU - Gu ZC AD - Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. AD - Drug Clinical Comprehensive Evaluation Group, Shanghai Pharmaceutical Association, Shanghai 200040, China. FAU - Lin, Hou-Wen AU - Lin HW AD - Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. LA - eng PT - Journal Article DEP - 20220701 PL - England TA - EClinicalMedicine JT - EClinicalMedicine JID - 101733727 PMC - PMC9256649 OTO - NOTNLM OT - Data mining OT - Drug adverse events OT - Immune checkpoint inhibitors OT - Lung cancer OT - Pharmacovigilance OT - Real-world data COIS- The authors have no conflicts of interest to declare. EDAT- 2022/07/12 06:00 MHDA- 2022/07/12 06:01 PMCR- 2022/07/01 CRDT- 2022/07/11 03:54 PHST- 2022/03/23 00:00 [received] PHST- 2022/06/07 00:00 [revised] PHST- 2022/06/08 00:00 [accepted] PHST- 2022/07/11 03:54 [entrez] PHST- 2022/07/12 06:00 [pubmed] PHST- 2022/07/12 06:01 [medline] PHST- 2022/07/01 00:00 [pmc-release] AID - S2589-5370(22)00265-6 [pii] AID - 101535 [pii] AID - 10.1016/j.eclinm.2022.101535 [doi] PST - epublish SO - EClinicalMedicine. 2022 Jul 1;50:101535. doi: 10.1016/j.eclinm.2022.101535. eCollection 2022 Aug.