Immune checkpoint inhibitors or anti-claudin 18.2 antibodies? A network meta-analysis for the optimized first-line therapy of HER2-negative gastric cancer
Background: Multiple anti-programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors and zolbetuximab, an anti-claudin 18.2 antibody, have shown efficacy in the first-line treatment of HER2-negative gastric cancers. How to choose the best regimen remains an unsolved question. Obj...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2024-02-01
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| Series: | Therapeutic Advances in Medical Oncology |
| Online Access: | https://doi.org/10.1177/17588359241231253 |
| _version_ | 1797276797070475264 |
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| author | Zhening Zhang Tong Xie Yingxuan Wang Lin Shen Xiaotian Zhang Zhi Peng |
| author_facet | Zhening Zhang Tong Xie Yingxuan Wang Lin Shen Xiaotian Zhang Zhi Peng |
| author_sort | Zhening Zhang |
| collection | DOAJ |
| description | Background: Multiple anti-programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors and zolbetuximab, an anti-claudin 18.2 antibody, have shown efficacy in the first-line treatment of HER2-negative gastric cancers. How to choose the best regimen remains an unsolved question. Objectives: We aimed to conduct a comparative analysis of the therapeutic advantages between immunotherapy and anti-claudin-18.2-targeted therapies in the first-line treatment of HER2-negative, unresectable, or metastatic gastric cancers. Design: Network meta-analysis was employed to systematically compare efficacy and safety data derived from various clinical trials. Data sources and methods: We included phase III randomized controlled trials in PubMed, Embase, Web of Science, Cochrane Library, and major conference abstracts. Network meta-analysis was used to compare the efficacy of each first-line therapeutic agent and to indirectly compare immunotherapy with anti-claudin-18.2-targeted therapy. Results: Eight trials comprising a total of 6455 patients were included. For the overall survival (OS) analysis, no statistically significant differences were observed between pembrolizumab [hazard ratios (HR) = 1.00, 95% CI: 0.94–1.07], sintilimab (HR = 0.99, 95% CI: 0.89–1.09), sugemalimab (HR = 0.98, 95% CI: 0.87–1.10), tislelizumab (HR = 0.97, 95% CI: 0.87–1.09), zolbetuximab (HR = 0.98, 95% CI: 0.91–1.07), and nivolumab (HR = 1.00). For the progression-free survival (PFS) analysis, no statistically significant differences were observed between pembrolizumab (HR = 1.00, 95% CI: 0.93–1.06), sintilimab (HR = 0.91, 95% CI: 0.83–1.00), sugemalimab (HR = 0.92, 95% CI: 0.84–1.02), tislelizumab (HR = 0.93, 95% CI: 0.84–1.03), zolbetuximab (HR = 0.96, 95% CI: 0.88–1.05), and nivolumab (HR = 1.00). For the overall response rate analysis, all regimens presented similar effects on ORR. In addition, anti-claudin-18.2-targeted therapies presented similar OS (HR = 0.99, 95% CI: 0.95–1.04) and PFS (HR = 1.01, 95% CI: 0.91–1.12) compared to immunotherapy, although their toxicity profiles were distinct. Conclusions: Our network meta-analysis showed no significant difference in PFS, OS, or ORR between different checkpoint inhibitors or between immunotherapy and anti-claudin-18.2-targeted therapies in the first-line treatment of HER2-negative, unresectable, or metastatic gastric cancers. |
| first_indexed | 2024-03-07T15:33:29Z |
| format | Article |
| id | doaj.art-39cd3d86304349f3a70116d30f776a44 |
| institution | Directory Open Access Journal |
| issn | 1758-8359 |
| language | English |
| last_indexed | 2024-03-07T15:33:29Z |
| publishDate | 2024-02-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Medical Oncology |
| spelling | doaj.art-39cd3d86304349f3a70116d30f776a442024-03-05T13:03:32ZengSAGE PublishingTherapeutic Advances in Medical Oncology1758-83592024-02-011610.1177/17588359241231253Immune checkpoint inhibitors or anti-claudin 18.2 antibodies? A network meta-analysis for the optimized first-line therapy of HER2-negative gastric cancerZhening ZhangTong XieYingxuan WangLin ShenXiaotian ZhangZhi PengBackground: Multiple anti-programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors and zolbetuximab, an anti-claudin 18.2 antibody, have shown efficacy in the first-line treatment of HER2-negative gastric cancers. How to choose the best regimen remains an unsolved question. Objectives: We aimed to conduct a comparative analysis of the therapeutic advantages between immunotherapy and anti-claudin-18.2-targeted therapies in the first-line treatment of HER2-negative, unresectable, or metastatic gastric cancers. Design: Network meta-analysis was employed to systematically compare efficacy and safety data derived from various clinical trials. Data sources and methods: We included phase III randomized controlled trials in PubMed, Embase, Web of Science, Cochrane Library, and major conference abstracts. Network meta-analysis was used to compare the efficacy of each first-line therapeutic agent and to indirectly compare immunotherapy with anti-claudin-18.2-targeted therapy. Results: Eight trials comprising a total of 6455 patients were included. For the overall survival (OS) analysis, no statistically significant differences were observed between pembrolizumab [hazard ratios (HR) = 1.00, 95% CI: 0.94–1.07], sintilimab (HR = 0.99, 95% CI: 0.89–1.09), sugemalimab (HR = 0.98, 95% CI: 0.87–1.10), tislelizumab (HR = 0.97, 95% CI: 0.87–1.09), zolbetuximab (HR = 0.98, 95% CI: 0.91–1.07), and nivolumab (HR = 1.00). For the progression-free survival (PFS) analysis, no statistically significant differences were observed between pembrolizumab (HR = 1.00, 95% CI: 0.93–1.06), sintilimab (HR = 0.91, 95% CI: 0.83–1.00), sugemalimab (HR = 0.92, 95% CI: 0.84–1.02), tislelizumab (HR = 0.93, 95% CI: 0.84–1.03), zolbetuximab (HR = 0.96, 95% CI: 0.88–1.05), and nivolumab (HR = 1.00). For the overall response rate analysis, all regimens presented similar effects on ORR. In addition, anti-claudin-18.2-targeted therapies presented similar OS (HR = 0.99, 95% CI: 0.95–1.04) and PFS (HR = 1.01, 95% CI: 0.91–1.12) compared to immunotherapy, although their toxicity profiles were distinct. Conclusions: Our network meta-analysis showed no significant difference in PFS, OS, or ORR between different checkpoint inhibitors or between immunotherapy and anti-claudin-18.2-targeted therapies in the first-line treatment of HER2-negative, unresectable, or metastatic gastric cancers.https://doi.org/10.1177/17588359241231253 |
| spellingShingle | Zhening Zhang Tong Xie Yingxuan Wang Lin Shen Xiaotian Zhang Zhi Peng Immune checkpoint inhibitors or anti-claudin 18.2 antibodies? A network meta-analysis for the optimized first-line therapy of HER2-negative gastric cancer Therapeutic Advances in Medical Oncology |
| title | Immune checkpoint inhibitors or anti-claudin 18.2 antibodies? A network meta-analysis for the optimized first-line therapy of HER2-negative gastric cancer |
| title_full | Immune checkpoint inhibitors or anti-claudin 18.2 antibodies? A network meta-analysis for the optimized first-line therapy of HER2-negative gastric cancer |
| title_fullStr | Immune checkpoint inhibitors or anti-claudin 18.2 antibodies? A network meta-analysis for the optimized first-line therapy of HER2-negative gastric cancer |
| title_full_unstemmed | Immune checkpoint inhibitors or anti-claudin 18.2 antibodies? A network meta-analysis for the optimized first-line therapy of HER2-negative gastric cancer |
| title_short | Immune checkpoint inhibitors or anti-claudin 18.2 antibodies? A network meta-analysis for the optimized first-line therapy of HER2-negative gastric cancer |
| title_sort | immune checkpoint inhibitors or anti claudin 18 2 antibodies a network meta analysis for the optimized first line therapy of her2 negative gastric cancer |
| url | https://doi.org/10.1177/17588359241231253 |
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