PMID- 37948860 OWN - NLM STAT- MEDLINE DCOM- 20231121 LR - 20231121 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 125 IP - Pt B DP - 2023 Dec TI - Clinical outcomes and immunological evaluation of toripalimab combination for cancer treatment: A systematic review and meta-analysis of randomized controlled trials. PG - 111176 LID - S1567-5769(23)01502-3 [pii] LID - 10.1016/j.intimp.2023.111176 [doi] AB - OBJECTIVE: This study was performed to evaluate the efficacy, safety and immunological function of toripalimab combination therapy, aiming to provide a reference for the clinical combined use of toripalimab and the development of subsequent indications for cancer treatment. MATERIALS AND METHODS: The meta-analysis was conducted by searching PubMed, Cochrane Library, Web of Science, EMBASE, CNKI database and Wanfang database until September 22, 2023. Only randomized controlled trials (RCTs) that involved cancer participants that received toripalimab combination therapy including a combination and control group were selected. The clinical outcomes of complete response rate (CR), objective response rate (ORR), overall survival (OS), progression-free survival (PFS), treatment related adverse effects (AEs) and immune-related adverse effects (irAEs) and immunological function index (CD3(+), CD4(+), CD8(+) and CD4(+)/CD8(+) T cells ratio) were extracted and evaluated. A random or fixed-effects models, as appropriate, were selected to calculate pooled effect estimates using Stata software (version 12.0). Subgroup analysis was done to estimate whether the effects of PD-L1 expression on PFS. Egger's test were carried out to measure publication bias. RESULTS: A total of 11 RCTs involving 1856 patients met the inclusion criteria. Both toripalimab plus chemotherapy and toripalimab plus targeted therapy had a trend of better CR [RR = 1.74, 95%CI (1.23, 2.45), P = 0.002], OS [HR = 1.94, 95%CI (1.76, 2.15), P < 0.001] and PFS [HR = 1.70, 95%CI (1.57, 1.83), P < 0.001], and an improvement of ORR [RR = 1.21, 95%CI (1.09, 1.35), P = 0.001] was found with toripalimab plus chemotherapy while not that plus targeted therapy compared to monotherapy. Subgroup analysis showed that toripalimab plus chemotherapy extended PFS whether PD-L1 positive or negative [HR = 1.78, 95%CI (1.60, 1.98), P < 0.001; HR = 1.60, 95%CI (1.37, 1.87), P < 0.001]. Additionally, toripalimab combined regimens significantly increased the proportion of CD3(+), CD4(+), and CD4(+)/CD8(+) T cells [SMD = 0.79, 95% CI (0.19, 1.40), p = 0.01; SMD = 1.40, 95% CI (0.72, 2.07), p < 0.001; SMD = 1.46, 95% CI (0.64, 2.28), p < 0.001]. The incidence of any grade [RR = 1.65, 95%CI (1.25, 2.18), P < 0.001] and grade 3 or worse irAEs [RR = 1.65, 95%CI (1.25, 2.18), P < 0.001] were higher with toripalimab combined regimens as compared to single treatment while no difference was found for treatment related AEs. Sensitivity analysis indicated that no individual study had influence on the pooled results. CONCLUSIONS: Based on the available data, both toripalimab plus chemotherapy and toripalimab plus targeted therapy demonstrated superior clinical outcomes and regulation of cellular immunity at the cost of greater but manageable toxicity. More clinical trials need to be performed to further evaluate the efficacy and safety for other toripalimab combined regimens. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Li, Jing AU - Li J AD - Pharmaceutical Department, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhang, Haiyan AU - Zhang H AD - Pharmaceutical Department, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. FAU - Zhu, Hongda AU - Zhu H AD - Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei Key Laboratory of Industrial Microbiology, National "111" Center for Cellular Regulation and Molecular Pharmaceutics, School of Food and Biological Engineering, Hubei University of Technology, Wuhan, China. Electronic address: bszzhuhongda@yeah.net. FAU - Li, Hongxia AU - Li H AD - Pharmaceutical Department, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: 593753467@qq.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20231108 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 8JXN261VVA (toripalimab) RN - 0 (B7-H1 Antigen) RN - 0 (Antibodies, Monoclonal, Humanized) SB - IM MH - Humans MH - B7-H1 Antigen MH - Randomized Controlled Trials as Topic MH - *Drug-Related Side Effects and Adverse Reactions MH - Antibodies, Monoclonal, Humanized/adverse effects MH - *Neoplasms/drug therapy OTO - NOTNLM OT - Adverse effects OT - Efficacy OT - Immunotherapy OT - Meta-analysis OT - Toripalimab COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/11/11 11:44 MHDA- 2023/11/21 06:42 CRDT- 2023/11/10 18:06 PHST- 2023/07/05 00:00 [received] PHST- 2023/10/19 00:00 [revised] PHST- 2023/11/01 00:00 [accepted] PHST- 2023/11/21 06:42 [medline] PHST- 2023/11/11 11:44 [pubmed] PHST- 2023/11/10 18:06 [entrez] AID - S1567-5769(23)01502-3 [pii] AID - 10.1016/j.intimp.2023.111176 [doi] PST - ppublish SO - Int Immunopharmacol. 2023 Dec;125(Pt B):111176. doi: 10.1016/j.intimp.2023.111176. Epub 2023 Nov 8.