Neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy in gastric cancer and gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis of single-arm studies
BackgroundNeoadjuvant chemotherapy, particularly neoadjuvant immunotherapy, has achieved significant progress in treating gastric cancer (GC) and gastroesophageal junction (GEJ) adenocarcinoma. While PD-1/PD-L1 inhibitors have improved survival outcomes in some patients, the efficacy of combining ne...
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Frontiers Media S.A.
2025-08-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2025.1625259/full |
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| author | Jun Leng Jun Leng Min Liu Min Liu Qianwen Wang Qianwen Wang Huaiwu Jiang Jin Chen |
| author_facet | Jun Leng Jun Leng Min Liu Min Liu Qianwen Wang Qianwen Wang Huaiwu Jiang Jin Chen |
| author_sort | Jun Leng |
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| description | BackgroundNeoadjuvant chemotherapy, particularly neoadjuvant immunotherapy, has achieved significant progress in treating gastric cancer (GC) and gastroesophageal junction (GEJ) adenocarcinoma. While PD-1/PD-L1 inhibitors have improved survival outcomes in some patients, the efficacy of combining neoadjuvant chemotherapy with PD-1/PD-L1 inhibitors remains insufficiently validated.ObjectiveThis study aims to evaluate the efficacy and safety of neoadjuvant chemotherapy combined with PD-1/PD-L1 inhibitors in GC/GEJ adenocarcinoma and enhance statistical power through meta-analysis.MethodsWe systematically searched PubMed, Embase, Web of Science, and the Cochrane Library up to October 5, 2024, for original clinical studies on neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy for GC/GEJ adenocarcinoma. Eligible studies were evaluated using the Methodological Index for Non-Randomized Studies (MINORS) Criteria. Meta-analysis was performed using R 4.4.2 software.ResultsA total of 12 studies involving 428 patients were included. The primary efficacy outcomes were pathological complete response (pCR) and major pathological response (MPR), while secondary outcomes included disease control rate (DCR) and the rate of lymph node downstaging to ypN0. The effect size (ES) for pCR was 20.94% [95% CI: 0.1698; 0.2518], and for MPR, the ES was 55.86% [95% CI: 0.4891; 0.6271]. Safety was evaluated using the incidence of grade ≥3 treatment-related adverse events (trAEs), immune-related adverse events (irAEs), postoperative complications, and R0 resection rate. The meta-analysis revealed that 406 patients underwent surgical intervention, with 88 achieving pCR. The pooled effect size for R0 resection rate was 95.2% [95% CI: 0.896; 0.989]. The ES values for grade ≥3 adverse events, immune-related adverse events, and postoperative complications were 0.54 [95% CI: 0.30; 0.77], 0.17 [95% CI: 0.07; 0.31], and 0.28 [95% CI: 0.15; 0.44], respectively.ConclusionNeoadjuvant PD-1/PD-L1 inhibitor-based chemotherapy demonstrates promising therapeutic efficacy and safety in patients with gastric and gastroesophageal junction (GEJ) cancer. However, limitations such as small sample sizes and insufficient follow-up duration in current studies highlight the need for further randomized controlled trials and multicenter research to establish optimal treatment strategies.Systamatic review registrationIdentifier, CRD42024619916. |
| format | Article |
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| institution | DOAJ |
| issn | 2296-858X |
| language | English |
| publishDate | 2025-08-01 |
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| spelling | doaj-art-5fb639c7fec742bf8dfd1f35be61b0572025-08-20T03:02:30ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2025-08-011210.3389/fmed.2025.16252591625259Neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy in gastric cancer and gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis of single-arm studiesJun Leng0Jun Leng1Min Liu2Min Liu3Qianwen Wang4Qianwen Wang5Huaiwu Jiang6Jin Chen7North Sichuan Medical College, Nanchong, Sichuan, ChinaDepartment of General Surgery, Mian Yang 404 Hospital, Mianyang, Sichuan, ChinaNorth Sichuan Medical College, Nanchong, Sichuan, ChinaDepartment of General Surgery, Mian Yang 404 Hospital, Mianyang, Sichuan, ChinaNorth Sichuan Medical College, Nanchong, Sichuan, ChinaDepartment of General Surgery, Mian Yang 404 Hospital, Mianyang, Sichuan, ChinaDepartment of Gastrointestinal Surgery, Mianyang Hospital, Mianyang, Sichuan, ChinaDepartment of General Surgery, Mian Yang 404 Hospital, Mianyang, Sichuan, ChinaBackgroundNeoadjuvant chemotherapy, particularly neoadjuvant immunotherapy, has achieved significant progress in treating gastric cancer (GC) and gastroesophageal junction (GEJ) adenocarcinoma. While PD-1/PD-L1 inhibitors have improved survival outcomes in some patients, the efficacy of combining neoadjuvant chemotherapy with PD-1/PD-L1 inhibitors remains insufficiently validated.ObjectiveThis study aims to evaluate the efficacy and safety of neoadjuvant chemotherapy combined with PD-1/PD-L1 inhibitors in GC/GEJ adenocarcinoma and enhance statistical power through meta-analysis.MethodsWe systematically searched PubMed, Embase, Web of Science, and the Cochrane Library up to October 5, 2024, for original clinical studies on neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy for GC/GEJ adenocarcinoma. Eligible studies were evaluated using the Methodological Index for Non-Randomized Studies (MINORS) Criteria. Meta-analysis was performed using R 4.4.2 software.ResultsA total of 12 studies involving 428 patients were included. The primary efficacy outcomes were pathological complete response (pCR) and major pathological response (MPR), while secondary outcomes included disease control rate (DCR) and the rate of lymph node downstaging to ypN0. The effect size (ES) for pCR was 20.94% [95% CI: 0.1698; 0.2518], and for MPR, the ES was 55.86% [95% CI: 0.4891; 0.6271]. Safety was evaluated using the incidence of grade ≥3 treatment-related adverse events (trAEs), immune-related adverse events (irAEs), postoperative complications, and R0 resection rate. The meta-analysis revealed that 406 patients underwent surgical intervention, with 88 achieving pCR. The pooled effect size for R0 resection rate was 95.2% [95% CI: 0.896; 0.989]. The ES values for grade ≥3 adverse events, immune-related adverse events, and postoperative complications were 0.54 [95% CI: 0.30; 0.77], 0.17 [95% CI: 0.07; 0.31], and 0.28 [95% CI: 0.15; 0.44], respectively.ConclusionNeoadjuvant PD-1/PD-L1 inhibitor-based chemotherapy demonstrates promising therapeutic efficacy and safety in patients with gastric and gastroesophageal junction (GEJ) cancer. However, limitations such as small sample sizes and insufficient follow-up duration in current studies highlight the need for further randomized controlled trials and multicenter research to establish optimal treatment strategies.Systamatic review registrationIdentifier, CRD42024619916.https://www.frontiersin.org/articles/10.3389/fmed.2025.1625259/fullcombination therapyefficacymeta-analysisneoadjuvant immunotherapygastric cancer/gastroesophageal junction tumorssafety |
| spellingShingle | Jun Leng Jun Leng Min Liu Min Liu Qianwen Wang Qianwen Wang Huaiwu Jiang Jin Chen Neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy in gastric cancer and gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis of single-arm studies Frontiers in Medicine combination therapy efficacy meta-analysis neoadjuvant immunotherapy gastric cancer/gastroesophageal junction tumors safety |
| title | Neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy in gastric cancer and gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis of single-arm studies |
| title_full | Neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy in gastric cancer and gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis of single-arm studies |
| title_fullStr | Neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy in gastric cancer and gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis of single-arm studies |
| title_full_unstemmed | Neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy in gastric cancer and gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis of single-arm studies |
| title_short | Neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy in gastric cancer and gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis of single-arm studies |
| title_sort | neoadjuvant pd 1 pd l1 inhibitors combined with chemotherapy in gastric cancer and gastroesophageal junction adenocarcinoma a systematic review and meta analysis of single arm studies |
| topic | combination therapy efficacy meta-analysis neoadjuvant immunotherapy gastric cancer/gastroesophageal junction tumors safety |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2025.1625259/full |
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