Rashid K Sayyid, Rui Bernardino, Julian Chavarriaga, Ravi Kumar, Harkanwal Randhawa, Marian S Wettstein, Jessica Grace Cockburn, Zachary Klaassen, Neil E Fleshner
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Pooled hazard ratios (HR) and relative risks (RR), plus confidence intervals (CI), were generated using frequentist random-effects modeling.</p><p><strong>Results: </strong>Three trials were identified: IMvigor010, CheckMate 274, and AMBASSADOR. In the overall cohort, adjuvant ICIs significantly improved DFS by 23% (HR = 0.77, 95% CI = 0.65-0.90). No DFS benefit was observed in patients with upper tract disease (HR = 1.19, 95% CI = 0.86-1.64). The highest magnitude of DFS benefit was observed among patients who had received prior neoadjuvant chemotherapy (HR = 0.69) and pathologic node-positive disease (HR = 0.75). A similar DFS benefit was observed irrespective of tumor PD-L1 status. Pooled OS demonstrated a 13% non-significant benefit (HR = 0.87, 95% CI = 0.75-1.01). Grade ≥ 3 immune-mediated AEs occurred in 8.6% and 2.1% of ICI and placebo/observation patients, respectively (RR = 4.35, 95% CI = 1.02-18.5). AEs leading to treatment discontinuation occurred in 14.3% and 0.9% of patients, respectively.</p><p><strong>Conclusion: </strong>Adjuvant ICIs confer a DFS benefit following radical surgery for MIUC, particularly among node-positive patients and those who received prior neoadjuvant chemotherapy. The lack of benefit for upper tract disease suggests that alternate adjuvant approaches, including chemotherapy, should be considered for these patients. Tumor PD-L1 status is not a predictive biomarker, highlighting the need for biomarkers in this setting.</p>","PeriodicalId":23954,"journal":{"name":"World Journal of Urology","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Adjuvant immune checkpoint inhibitors for urothelial carcinoma: systematic review and Meta-analysis.\",\"authors\":\"Rashid K Sayyid, Rui Bernardino, Julian Chavarriaga, Ravi Kumar, Harkanwal Randhawa, Marian S Wettstein, Jessica Grace Cockburn, Zachary Klaassen, Neil E Fleshner\",\"doi\":\"10.1007/s00345-024-05147-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>To compare disease-free survival (DFS), overall survival (OS), and adverse events (AEs) among muscle-invasive urothelial carcinoma (MIUC) patients receiving adjuvant immune checkpoint inhibitors (ICIs) versus placebo/observation following radical surgery.</p><p><strong>Methods: </strong>This was a systematic review/meta-analysis of all published phase 3 randomized controlled trials. MEDLINE, EMBASE, and Cochrane were searched from inception until April 4, 2024. Pooled hazard ratios (HR) and relative risks (RR), plus confidence intervals (CI), were generated using frequentist random-effects modeling.</p><p><strong>Results: </strong>Three trials were identified: IMvigor010, CheckMate 274, and AMBASSADOR. In the overall cohort, adjuvant ICIs significantly improved DFS by 23% (HR = 0.77, 95% CI = 0.65-0.90). No DFS benefit was observed in patients with upper tract disease (HR = 1.19, 95% CI = 0.86-1.64). The highest magnitude of DFS benefit was observed among patients who had received prior neoadjuvant chemotherapy (HR = 0.69) and pathologic node-positive disease (HR = 0.75). A similar DFS benefit was observed irrespective of tumor PD-L1 status. Pooled OS demonstrated a 13% non-significant benefit (HR = 0.87, 95% CI = 0.75-1.01). Grade ≥ 3 immune-mediated AEs occurred in 8.6% and 2.1% of ICI and placebo/observation patients, respectively (RR = 4.35, 95% CI = 1.02-18.5). AEs leading to treatment discontinuation occurred in 14.3% and 0.9% of patients, respectively.</p><p><strong>Conclusion: </strong>Adjuvant ICIs confer a DFS benefit following radical surgery for MIUC, particularly among node-positive patients and those who received prior neoadjuvant chemotherapy. The lack of benefit for upper tract disease suggests that alternate adjuvant approaches, including chemotherapy, should be considered for these patients. Tumor PD-L1 status is not a predictive biomarker, highlighting the need for biomarkers in this setting.</p>\",\"PeriodicalId\":23954,\"journal\":{\"name\":\"World Journal of Urology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-07-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"World Journal of Urology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00345-024-05147-2\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Journal of Urology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00345-024-05147-2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的:比较根治术后接受辅助免疫检查点抑制剂(ICIs)与安慰剂/观察的肌浸润性尿路上皮癌(MIUC)患者的无病生存期(DFS)、总生存期(OS)和不良事件(AEs):这是对所有已发表的三期随机对照试验进行的系统综述/荟萃分析。检索了从开始到2024年4月4日的MEDLINE、EMBASE和Cochrane。采用频数随机效应模型生成汇总的危险比(HR)和相对危险度(RR)以及置信区间(CI):结果:确定了三项试验:结果:确定了三项试验:IMvigor010、CheckMate 274 和 AMBASSADOR。在总体队列中,辅助 ICIs 可使 DFS 明显改善 23%(HR = 0.77,95% CI = 0.65-0.90)。在上消化道疾病患者中未观察到DFS获益(HR = 1.19,95% CI = 0.86-1.64)。在既往接受过新辅助化疗(HR = 0.69)和病理结节阳性疾病(HR = 0.75)的患者中,DFS获益程度最高。无论肿瘤的PD-L1状态如何,都能观察到相似的DFS获益。汇总的OS显示有13%的非显著获益(HR = 0.87,95% CI = 0.75-1.01)。ICI 和安慰剂/观察组患者中分别有 8.6% 和 2.1% 出现≥3 级免疫介导的 AEs(RR = 4.35,95% CI = 1.02-18.5)。分别有14.3%和0.9%的患者出现了导致治疗中断的AEs:结论:MIUC根治术后,辅助ICIs可带来DFS获益,尤其是在结节阳性患者和之前接受过新辅助化疗的患者中。对上道疾病没有益处表明,这些患者应考虑采用包括化疗在内的其他辅助方法。肿瘤PD-L1状态并不是一种预测性生物标志物,这凸显了在这种情况下对生物标志物的需求。
Adjuvant immune checkpoint inhibitors for urothelial carcinoma: systematic review and Meta-analysis.
Purpose: To compare disease-free survival (DFS), overall survival (OS), and adverse events (AEs) among muscle-invasive urothelial carcinoma (MIUC) patients receiving adjuvant immune checkpoint inhibitors (ICIs) versus placebo/observation following radical surgery.
Methods: This was a systematic review/meta-analysis of all published phase 3 randomized controlled trials. MEDLINE, EMBASE, and Cochrane were searched from inception until April 4, 2024. Pooled hazard ratios (HR) and relative risks (RR), plus confidence intervals (CI), were generated using frequentist random-effects modeling.
Results: Three trials were identified: IMvigor010, CheckMate 274, and AMBASSADOR. In the overall cohort, adjuvant ICIs significantly improved DFS by 23% (HR = 0.77, 95% CI = 0.65-0.90). No DFS benefit was observed in patients with upper tract disease (HR = 1.19, 95% CI = 0.86-1.64). The highest magnitude of DFS benefit was observed among patients who had received prior neoadjuvant chemotherapy (HR = 0.69) and pathologic node-positive disease (HR = 0.75). A similar DFS benefit was observed irrespective of tumor PD-L1 status. Pooled OS demonstrated a 13% non-significant benefit (HR = 0.87, 95% CI = 0.75-1.01). Grade ≥ 3 immune-mediated AEs occurred in 8.6% and 2.1% of ICI and placebo/observation patients, respectively (RR = 4.35, 95% CI = 1.02-18.5). AEs leading to treatment discontinuation occurred in 14.3% and 0.9% of patients, respectively.
Conclusion: Adjuvant ICIs confer a DFS benefit following radical surgery for MIUC, particularly among node-positive patients and those who received prior neoadjuvant chemotherapy. The lack of benefit for upper tract disease suggests that alternate adjuvant approaches, including chemotherapy, should be considered for these patients. Tumor PD-L1 status is not a predictive biomarker, highlighting the need for biomarkers in this setting.
期刊介绍:
The WORLD JOURNAL OF UROLOGY conveys regularly the essential results of urological research and their practical and clinical relevance to a broad audience of urologists in research and clinical practice. In order to guarantee a balanced program, articles are published to reflect the developments in all fields of urology on an internationally advanced level. Each issue treats a main topic in review articles of invited international experts. Free papers are unrelated articles to the main topic.