M S Beshr, I A Beshr, M Al Hayek, S M Alfaqaih, M Abuajamieh, E Basheer, A K Wali, M Ekreer, I Chenfouh, A Khashan, E T Hassan, S M Elnaami, M Elhadi
{"title":"PD-1/PD-L1抑制剂与化疗联合或单药治疗晚期不可切除的HER2阴性胃癌、胃食管交界癌和食管腺癌与单用化疗的对比：一项Meta分析。","authors":"M S Beshr, I A Beshr, M Al Hayek, S M Alfaqaih, M Abuajamieh, E Basheer, A K Wali, M Ekreer, I Chenfouh, A Khashan, E T Hassan, S M Elnaami, M Elhadi","doi":"10.1016/j.clon.2024.09.007","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>Advanced gastroesophageal cancers are still associated with poor outcomes. We aim to study PD-1/PD-L1 inhibitors in phase III clinical trials that have compared them to chemotherapy in gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma.</p><p><strong>Materials and methods: </strong>On March 28, 2024, we searched: PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov. We only included randomized clinical trials for PD-1/PD-L1 inhibitors alone or with chemo vs chemotherapy in advanced gastric, GEJ, or esophageal adenocarcinoma. The primary endpoints were overall survival and progression-free survival. A subgroup analysis was conducted for the following variables: treatment line, type of intervention, age group, gender, ECOG Performance Status, combined positive scores (CPS), microsatellite instability (MSI) status, liver metastasis, and primary tumor location.</p><p><strong>Results: </strong>Only 10 out of 8,942 articles were included, involving 6,782 patients. PD-1/PD-L1 inhibitors showed a significant improvement in the overall survival compared to chemotherapy alone (hazard ratio (HR): 0.86, 95% CI: 0.80-0.93; p = 0.0002). Combining PD-1/PD-L1 inhibitors with chemotherapy significantly improved overall and progression-free survival compared to monotherapy (combined therapy HR 0.80; p < 0.00001 vs. monotherapy HR 0.98; p = 0.77). CPS ≥1 had an HR of 0.78 (95% CI: 0.73-0.84; p < 0.00001), CPS ≥10 had an HR of 0.67 (95% CI: 0.59-0.76; p < 0.00001), and MSI-high status had an HR of 0.35 (95% CI: 0.24-0.52; p < 0.00001). Esophageal adenocarcinoma, reported in three trials, did not show significant improvement in the overall survival (HR 0.89; 95% CI: 0.69-1.14; p = 0.37).</p><p><strong>Conclusion: </strong>PD-1/PD-L1 inhibitors have significantly improved overall survival, and combining them with chemotherapy is more effective than monotherapy. Both CPS ≥10 and MSI-H showed an added benefit to overall survival and should be included in biomarker investigations. Clinical trials are needed for second-line treatments and esophageal adenocarcinoma.</p>","PeriodicalId":10403,"journal":{"name":"Clinical oncology","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"PD-1/PD-L1 Inhibitors in Combination With Chemo or as Monotherapy vs. Chemotherapy Alone in Advanced, Unresectable HER2-Negative Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: A Meta-Analysis.\",\"authors\":\"M S Beshr, I A Beshr, M Al Hayek, S M Alfaqaih, M Abuajamieh, E Basheer, A K Wali, M Ekreer, I Chenfouh, A Khashan, E T Hassan, S M Elnaami, M Elhadi\",\"doi\":\"10.1016/j.clon.2024.09.007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>Advanced gastroesophageal cancers are still associated with poor outcomes. We aim to study PD-1/PD-L1 inhibitors in phase III clinical trials that have compared them to chemotherapy in gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma.</p><p><strong>Materials and methods: </strong>On March 28, 2024, we searched: PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov. We only included randomized clinical trials for PD-1/PD-L1 inhibitors alone or with chemo vs chemotherapy in advanced gastric, GEJ, or esophageal adenocarcinoma. The primary endpoints were overall survival and progression-free survival. A subgroup analysis was conducted for the following variables: treatment line, type of intervention, age group, gender, ECOG Performance Status, combined positive scores (CPS), microsatellite instability (MSI) status, liver metastasis, and primary tumor location.</p><p><strong>Results: </strong>Only 10 out of 8,942 articles were included, involving 6,782 patients. PD-1/PD-L1 inhibitors showed a significant improvement in the overall survival compared to chemotherapy alone (hazard ratio (HR): 0.86, 95% CI: 0.80-0.93; p = 0.0002). Combining PD-1/PD-L1 inhibitors with chemotherapy significantly improved overall and progression-free survival compared to monotherapy (combined therapy HR 0.80; p < 0.00001 vs. monotherapy HR 0.98; p = 0.77). CPS ≥1 had an HR of 0.78 (95% CI: 0.73-0.84; p < 0.00001), CPS ≥10 had an HR of 0.67 (95% CI: 0.59-0.76; p < 0.00001), and MSI-high status had an HR of 0.35 (95% CI: 0.24-0.52; p < 0.00001). Esophageal adenocarcinoma, reported in three trials, did not show significant improvement in the overall survival (HR 0.89; 95% CI: 0.69-1.14; p = 0.37).</p><p><strong>Conclusion: </strong>PD-1/PD-L1 inhibitors have significantly improved overall survival, and combining them with chemotherapy is more effective than monotherapy. Both CPS ≥10 and MSI-H showed an added benefit to overall survival and should be included in biomarker investigations. Clinical trials are needed for second-line treatments and esophageal adenocarcinoma.</p>\",\"PeriodicalId\":10403,\"journal\":{\"name\":\"Clinical oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-09-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.clon.2024.09.007\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.clon.2024.09.007","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
PD-1/PD-L1 Inhibitors in Combination With Chemo or as Monotherapy vs. Chemotherapy Alone in Advanced, Unresectable HER2-Negative Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: A Meta-Analysis.
Aims: Advanced gastroesophageal cancers are still associated with poor outcomes. We aim to study PD-1/PD-L1 inhibitors in phase III clinical trials that have compared them to chemotherapy in gastric, gastroesophageal junction (GEJ), and esophageal adenocarcinoma.
Materials and methods: On March 28, 2024, we searched: PubMed, Embase, Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov. We only included randomized clinical trials for PD-1/PD-L1 inhibitors alone or with chemo vs chemotherapy in advanced gastric, GEJ, or esophageal adenocarcinoma. The primary endpoints were overall survival and progression-free survival. A subgroup analysis was conducted for the following variables: treatment line, type of intervention, age group, gender, ECOG Performance Status, combined positive scores (CPS), microsatellite instability (MSI) status, liver metastasis, and primary tumor location.
Results: Only 10 out of 8,942 articles were included, involving 6,782 patients. PD-1/PD-L1 inhibitors showed a significant improvement in the overall survival compared to chemotherapy alone (hazard ratio (HR): 0.86, 95% CI: 0.80-0.93; p = 0.0002). Combining PD-1/PD-L1 inhibitors with chemotherapy significantly improved overall and progression-free survival compared to monotherapy (combined therapy HR 0.80; p < 0.00001 vs. monotherapy HR 0.98; p = 0.77). CPS ≥1 had an HR of 0.78 (95% CI: 0.73-0.84; p < 0.00001), CPS ≥10 had an HR of 0.67 (95% CI: 0.59-0.76; p < 0.00001), and MSI-high status had an HR of 0.35 (95% CI: 0.24-0.52; p < 0.00001). Esophageal adenocarcinoma, reported in three trials, did not show significant improvement in the overall survival (HR 0.89; 95% CI: 0.69-1.14; p = 0.37).
Conclusion: PD-1/PD-L1 inhibitors have significantly improved overall survival, and combining them with chemotherapy is more effective than monotherapy. Both CPS ≥10 and MSI-H showed an added benefit to overall survival and should be included in biomarker investigations. Clinical trials are needed for second-line treatments and esophageal adenocarcinoma.
期刊介绍：
Clinical Oncology is an International cancer journal covering all aspects of the clinical management of cancer patients, reflecting a multidisciplinary approach to therapy. Papers, editorials and reviews are published on all types of malignant disease embracing, pathology, diagnosis and treatment, including radiotherapy, chemotherapy, surgery, combined modality treatment and palliative care. Research and review papers covering epidemiology, radiobiology, radiation physics, tumour biology, and immunology are also published, together with letters to the editor, case reports and book reviews.
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