Clinical outcomes and immunological evaluation of toripalimab combination for cancer treatment : A systematic review and meta-analysis of randomized controlled trials
Copyright © 2023 Elsevier B.V. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:125 |
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| Enthalten in: |
International immunopharmacology - 125(2023), Pt B vom: 10. Dez., Seite 111176 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Jing [VerfasserIn] |
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| Links: |
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| Themen: |
8JXN261VVA |
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| Anmerkungen: |
Date Completed 21.11.2023 Date Revised 21.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.intimp.2023.111176 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364405244 |
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| 100 | 1 | |a Li, Jing |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Clinical outcomes and immunological evaluation of toripalimab combination for cancer treatment |b A systematic review and meta-analysis of randomized controlled trials |
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| 500 | |a Date Revised 21.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier B.V. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Meta-Analysis | |
| 650 | 4 | |a Systematic Review | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a Adverse effects | |
| 650 | 4 | |a Efficacy | |
| 650 | 4 | |a Immunotherapy | |
| 650 | 4 | |a Meta-analysis | |
| 650 | 4 | |a Toripalimab | |
| 650 | 7 | |a toripalimab |2 NLM | |
| 650 | 7 | |a 8JXN261VVA |2 NLM | |
| 650 | 7 | |a B7-H1 Antigen |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 700 | 1 | |a Zhang, Haiyan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Hongda |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hongxia |e verfasserin |4 aut | |
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