The efficacy and safety of combination of PD-1 and CTLA-4 inhibitors: a meta-analysis
Abstract Background Recently, a series of clinical trials showed that combination of anti-programmed cell death-1 (α-PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (α-CTLA-4) could effectively eliminate tumor. However, in comparison with widely adopted mono-immune checkpoint inhibitors,...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-10-01
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| Series: | Experimental Hematology & Oncology |
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| Online Access: | http://link.springer.com/article/10.1186/s40164-019-0150-0 |
| _version_ | 1818198905437814784 |
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| author | Kongju Wu Ming Yi Shuang Qin Qian Chu Xinhua Zheng Kongming Wu |
| author_facet | Kongju Wu Ming Yi Shuang Qin Qian Chu Xinhua Zheng Kongming Wu |
| author_sort | Kongju Wu |
| collection | DOAJ |
| description | Abstract Background Recently, a series of clinical trials showed that combination of anti-programmed cell death-1 (α-PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (α-CTLA-4) could effectively eliminate tumor. However, in comparison with widely adopted mono-immune checkpoint inhibitors, chemotherapy, and targeted therapy, the advantage of combination therapy of α-PD-1 and α-CTLA-4 in response rate and prognosis is controversial especially considering probably increased treatment related adverse event. Thus, we conducted this meta-analysis to explore the efficacy and safety of combination treatment of α-PD-1 and α-CTLA-4. Methods This meta-analysis involved 8 clinical trials. In most trials, the primary endpoint was objective response rate (ORR). Thus we calculated risk ratio (RR) and 95% confidence interval (CI) to compare ORR of patients undergoing different treatment strategies. Moreover, the co-primary endpoints in few trials included progression-free survival and overall survival. Hazard ratio (HR) with 95% CI were employed to weigh the influence of different treatments on prognosis of patients. Subgroup analysis was conducted in patients with high and low expression of PD-L1. Lastly, the safety of combination therapy was evaluated by comparing treatment related adverse events among various treatment groups. Results Our results showed that ORR was significantly higher in patients receiving α-PD-1 plus α-CTLA-4 compared with α-PD-1 (RR 1.31, 95% CI 1.16–1.48) or α-CTLA-4 monotherapy (RR 2.11, 95% CI 1.84–2.43), chemotherapy and targeted therapy (RR 1.41, 95% CI 1.26–1.58). α-PD-1 plus α-CTLA-4 treated patients had a great advantage on monotherapy, chemotherapy and targeted therapy treated patients in PFS. Notably, no significant alteration in total adverse event rate was observed in α-PD-1 plus α-CTLA-4 treated patients. Results of subgroup analysis showed that combination therapy could enhance anti-tumor response in comparison with other treatments, especially for low PD-L1 expression patients undergoing nivolumab treatment (ORR: RR 1.35, 95% CI 1.11–1.65). Conclusion Combination treatment of α-PD-1 and α-CTLA-4 is a feasible strategy with enhanced efficacy and acceptable adverse event. Moreover, for some low PD-L1 expression patients, α-CTLA-4 might decrease the risk of resistance to α-PD-1 and demonstrate the synergistic anti-tumor effect. |
| first_indexed | 2024-12-12T02:13:18Z |
| format | Article |
| id | doaj.art-782055b50ce746a08c9d81159358eab7 |
| institution | Directory Open Access Journal |
| issn | 2162-3619 |
| language | English |
| last_indexed | 2024-12-12T02:13:18Z |
| publishDate | 2019-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Experimental Hematology & Oncology |
| spelling | doaj.art-782055b50ce746a08c9d81159358eab72022-12-22T00:41:51ZengBMCExperimental Hematology & Oncology2162-36192019-10-018111210.1186/s40164-019-0150-0The efficacy and safety of combination of PD-1 and CTLA-4 inhibitors: a meta-analysisKongju Wu0Ming Yi1Shuang Qin2Qian Chu3Xinhua Zheng4Kongming Wu5Department of Clinical Medicine, Medical School of Pingdingshan UniversityDepartment of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Clinical Medicine, Medical School of Pingdingshan UniversityDepartment of Clinical Medicine, Medical School of Pingdingshan UniversityAbstract Background Recently, a series of clinical trials showed that combination of anti-programmed cell death-1 (α-PD-1) and anti-cytotoxic T-lymphocyte-associated protein 4 (α-CTLA-4) could effectively eliminate tumor. However, in comparison with widely adopted mono-immune checkpoint inhibitors, chemotherapy, and targeted therapy, the advantage of combination therapy of α-PD-1 and α-CTLA-4 in response rate and prognosis is controversial especially considering probably increased treatment related adverse event. Thus, we conducted this meta-analysis to explore the efficacy and safety of combination treatment of α-PD-1 and α-CTLA-4. Methods This meta-analysis involved 8 clinical trials. In most trials, the primary endpoint was objective response rate (ORR). Thus we calculated risk ratio (RR) and 95% confidence interval (CI) to compare ORR of patients undergoing different treatment strategies. Moreover, the co-primary endpoints in few trials included progression-free survival and overall survival. Hazard ratio (HR) with 95% CI were employed to weigh the influence of different treatments on prognosis of patients. Subgroup analysis was conducted in patients with high and low expression of PD-L1. Lastly, the safety of combination therapy was evaluated by comparing treatment related adverse events among various treatment groups. Results Our results showed that ORR was significantly higher in patients receiving α-PD-1 plus α-CTLA-4 compared with α-PD-1 (RR 1.31, 95% CI 1.16–1.48) or α-CTLA-4 monotherapy (RR 2.11, 95% CI 1.84–2.43), chemotherapy and targeted therapy (RR 1.41, 95% CI 1.26–1.58). α-PD-1 plus α-CTLA-4 treated patients had a great advantage on monotherapy, chemotherapy and targeted therapy treated patients in PFS. Notably, no significant alteration in total adverse event rate was observed in α-PD-1 plus α-CTLA-4 treated patients. Results of subgroup analysis showed that combination therapy could enhance anti-tumor response in comparison with other treatments, especially for low PD-L1 expression patients undergoing nivolumab treatment (ORR: RR 1.35, 95% CI 1.11–1.65). Conclusion Combination treatment of α-PD-1 and α-CTLA-4 is a feasible strategy with enhanced efficacy and acceptable adverse event. Moreover, for some low PD-L1 expression patients, α-CTLA-4 might decrease the risk of resistance to α-PD-1 and demonstrate the synergistic anti-tumor effect.http://link.springer.com/article/10.1186/s40164-019-0150-0ImmunotherapyPD-1PD-L1CTLA-4Immune checkpoint inhibitorCombination therapy |
| spellingShingle | Kongju Wu Ming Yi Shuang Qin Qian Chu Xinhua Zheng Kongming Wu The efficacy and safety of combination of PD-1 and CTLA-4 inhibitors: a meta-analysis Experimental Hematology & Oncology Immunotherapy PD-1 PD-L1 CTLA-4 Immune checkpoint inhibitor Combination therapy |
| title | The efficacy and safety of combination of PD-1 and CTLA-4 inhibitors: a meta-analysis |
| title_full | The efficacy and safety of combination of PD-1 and CTLA-4 inhibitors: a meta-analysis |
| title_fullStr | The efficacy and safety of combination of PD-1 and CTLA-4 inhibitors: a meta-analysis |
| title_full_unstemmed | The efficacy and safety of combination of PD-1 and CTLA-4 inhibitors: a meta-analysis |
| title_short | The efficacy and safety of combination of PD-1 and CTLA-4 inhibitors: a meta-analysis |
| title_sort | efficacy and safety of combination of pd 1 and ctla 4 inhibitors a meta analysis |
| topic | Immunotherapy PD-1 PD-L1 CTLA-4 Immune checkpoint inhibitor Combination therapy |
| url | http://link.springer.com/article/10.1186/s40164-019-0150-0 |
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