Neoadjuvant PD-1/PD-L1 combined with CTLA-4 inhibitors for solid malignancies: a systematic review and meta-analysis
Abstract Background The effectiveness and safety of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors is controversial. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors as neoadjuvant therapy f...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | World Journal of Surgical Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12957-023-03212-5 |
| _version_ | 1797630192170041344 |
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| author | Shuang Huang Gang Zheng Kai Yang |
| author_facet | Shuang Huang Gang Zheng Kai Yang |
| author_sort | Shuang Huang |
| collection | DOAJ |
| description | Abstract Background The effectiveness and safety of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors is controversial. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors as neoadjuvant therapy for malignant solid tumors. Methods This study has been registered with the number CRD42023407275 on PROSPERO. Systematic searches were conducted in PubMed, Embase, Web of Science and Cochrane Library databases until March 17, 2023. In addition, manual searches were performed. The inclusion criteria encompassed randomized controlled trials (RCTs) that assessed the utilization of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors PD-1/PD-L1 inhibitors for patients with solid malignancies. The Cochrane Collaboration's tool for assessing risk of bias in randomized trials (ROB1) were used. Risk ratios (RRs), hazared ratios (HRs) and their respective 95% confidence intervals were calculated using Stata17.0 MP and Review Manager 5.4 software. Results A total of 2780 records were identified, and ultimately 10 studies involving 273 patients were included. The meta-analysis showed that the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors did not demonstrate a significant effect on overall response rate, main pathological response, pathological complete response, surgical resection, radical resection, overall survival, progression-free survival, recurrence-free survival, grade 3–4 adverse events, all-cause mortality, and completed treatment (P > 0.05). However, further subgroup analysis indicated that the combination of PD-1 with CTLA-4 inhibitors significantly increased the occurrence of grade 3–4 adverse events in patients (P < 0.05). Conclusions As neoadjuvant therapy for malignant solid tumors, the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors does not appear to enhance efficacy.Moreover, there is a potential increase in the risk of grade 3–4 adverse events associated with this combination. However, it is important to note that the studies included in this analysis suffer from limitations such as small samples and single-center designs, which are inherent constrains with the available published literature. Further research involving large-sample and multicenter RCTs are warranted to obtain more reliable results. |
| first_indexed | 2024-03-11T11:04:43Z |
| format | Article |
| id | doaj.art-c920b5bcaf234051a4c52b2f5a279786 |
| institution | Directory Open Access Journal |
| issn | 1477-7819 |
| language | English |
| last_indexed | 2024-03-11T11:04:43Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | World Journal of Surgical Oncology |
| spelling | doaj.art-c920b5bcaf234051a4c52b2f5a2797862023-11-12T12:19:38ZengBMCWorld Journal of Surgical Oncology1477-78192023-11-0121111110.1186/s12957-023-03212-5Neoadjuvant PD-1/PD-L1 combined with CTLA-4 inhibitors for solid malignancies: a systematic review and meta-analysisShuang Huang0Gang Zheng1Kai Yang2Department of Stomatology, Shapingba Hospital affiliated to Chongqing UniversityAnorectal Department, Chongqing Traditional Chinese Medicine HospitalDepartment of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical UniversityAbstract Background The effectiveness and safety of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors is controversial. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors as neoadjuvant therapy for malignant solid tumors. Methods This study has been registered with the number CRD42023407275 on PROSPERO. Systematic searches were conducted in PubMed, Embase, Web of Science and Cochrane Library databases until March 17, 2023. In addition, manual searches were performed. The inclusion criteria encompassed randomized controlled trials (RCTs) that assessed the utilization of neoadjuvant PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors PD-1/PD-L1 inhibitors for patients with solid malignancies. The Cochrane Collaboration's tool for assessing risk of bias in randomized trials (ROB1) were used. Risk ratios (RRs), hazared ratios (HRs) and their respective 95% confidence intervals were calculated using Stata17.0 MP and Review Manager 5.4 software. Results A total of 2780 records were identified, and ultimately 10 studies involving 273 patients were included. The meta-analysis showed that the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors did not demonstrate a significant effect on overall response rate, main pathological response, pathological complete response, surgical resection, radical resection, overall survival, progression-free survival, recurrence-free survival, grade 3–4 adverse events, all-cause mortality, and completed treatment (P > 0.05). However, further subgroup analysis indicated that the combination of PD-1 with CTLA-4 inhibitors significantly increased the occurrence of grade 3–4 adverse events in patients (P < 0.05). Conclusions As neoadjuvant therapy for malignant solid tumors, the addition of CTLA-4 inhibitors to PD-1/PD-L1 inhibitors does not appear to enhance efficacy.Moreover, there is a potential increase in the risk of grade 3–4 adverse events associated with this combination. However, it is important to note that the studies included in this analysis suffer from limitations such as small samples and single-center designs, which are inherent constrains with the available published literature. Further research involving large-sample and multicenter RCTs are warranted to obtain more reliable results.https://doi.org/10.1186/s12957-023-03212-5Neoadjuvant therapyImmune checkpoint inhibitorsPD-1PD-L1CTLA-4Meta-analysis |
| spellingShingle | Shuang Huang Gang Zheng Kai Yang Neoadjuvant PD-1/PD-L1 combined with CTLA-4 inhibitors for solid malignancies: a systematic review and meta-analysis World Journal of Surgical Oncology Neoadjuvant therapy Immune checkpoint inhibitors PD-1 PD-L1 CTLA-4 Meta-analysis |
| title | Neoadjuvant PD-1/PD-L1 combined with CTLA-4 inhibitors for solid malignancies: a systematic review and meta-analysis |
| title_full | Neoadjuvant PD-1/PD-L1 combined with CTLA-4 inhibitors for solid malignancies: a systematic review and meta-analysis |
| title_fullStr | Neoadjuvant PD-1/PD-L1 combined with CTLA-4 inhibitors for solid malignancies: a systematic review and meta-analysis |
| title_full_unstemmed | Neoadjuvant PD-1/PD-L1 combined with CTLA-4 inhibitors for solid malignancies: a systematic review and meta-analysis |
| title_short | Neoadjuvant PD-1/PD-L1 combined with CTLA-4 inhibitors for solid malignancies: a systematic review and meta-analysis |
| title_sort | neoadjuvant pd 1 pd l1 combined with ctla 4 inhibitors for solid malignancies a systematic review and meta analysis |
| topic | Neoadjuvant therapy Immune checkpoint inhibitors PD-1 PD-L1 CTLA-4 Meta-analysis |
| url | https://doi.org/10.1186/s12957-023-03212-5 |
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