PD-L1 thresholds predict efficacy of immune checkpoint inhibition in first-line treatment of advanced gastroesophageal adenocarcinoma. A systematic review and meta-analysis of seven phase III randomized trials

IF 7.1 2区医学 Q1 ONCOLOGY

ESMO Open Pub Date : 2024-11-01 DOI:10.1016/j.esmoop.2024.103967

V. Formica , C. Morelli , L. Fornaro , S. Riondino , M. Rofei , E. Fontana , E.C. Smyth , M. Roselli , H.-T. Arkenau

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引用次数: 0

Abstract

Background

High expression of programmed death-ligand 1 (PD-L1) has been recognized as a marker of improved efficacy of immunotherapy in gastroesophageal adenocarcinoma (GEA); however, the optimal PD-L1 cut-off is still debated. The aim of the present review was to analyze available phase III trials and to identify the appropriate PD-L1 expression cut-off for GEA.

Methods

Phase III trials investigating the efficacy of anti-programmed cell death protein 1 (PD-1) therapies in addition to standard chemotherapy versus standard chemotherapy in the first-line setting were selected. Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) were the analyzed outcome measures. Pooled treatment effects were assessed in the unselected population and in subpopulations with different levels of PD-L1 expression.

Results

PD-1 blockade efficacy was found to consistently increase in a linear manner with higher combined positive score (CPS) of PD-L1 expression: pooled hazard ratio (HR) for OS and PFS and pooled odds ratio (OR) for ORR of 0.80, 0.75 and 1.51, respectively, in the unselected population versus 0.67, 0.63 and 1.90, respectively, in the CPS ≥10 population (all P values < 0.0001). In the PD-L1-negative population (CPS <1) a significant benefit of anti-PD-1 agents could not be demonstrated in terms of OS and PFS (P = 0.28 and 0.12, respectively), but it was seen in terms of ORR (P = 0.03). PD-1 blockade was effective in the CPS <10 population (P value for pooled OS HR, PFS HR and response OR are all 0.01), while in the CPS <5 population the effect was of borderline significance for OS (P = 0.07) and significant for PFS and ORR (P = 0.02 and 0.03, respectively).

Conclusion

The present meta-analysis confirmed that the benefit of PD-1 blockade in GEA patients is related to PD-L1 CPS, with increased benefit observed for higher CPS cut-offs and no OS benefit in the CPS <1 subset. Overall, data indicate that PD-L1 CPS ≥5 could represent an acceptable cut-off to optimize the risk/benefit ratio of such agents. Our data suggest a potential clinical benefit of immunotherapy in selected patients within the CPS 1-4 population which needs further investigation.

查看原文本刊更多论文

PD-L1阈值可预测免疫检查点抑制剂在晚期胃食管腺癌一线治疗中的疗效。七项III期随机试验的系统回顾和荟萃分析。

背景：程序性死亡配体1（PD-L1）的高表达已被认为是提高胃食管腺癌（GEA）免疫疗法疗效的标志；然而，PD-L1的最佳临界值仍存在争议。本综述旨在分析现有的III期试验，并确定适合GEA的PD-L1表达临界值：方法：选取了研究抗程序性细胞死亡蛋白1（PD-1）疗法在标准化疗基础上对一线标准化疗疗效的III期试验。无进展生存期（PFS）、总生存期（OS）和客观反应率（ORR）是分析的结局指标。在未入选人群和PD-L1表达水平不同的亚人群中评估了汇总治疗效果：结果发现，PD-1阻断疗效随着PD-L1表达联合阳性评分（CPS）的升高而呈线性增长：在未入选人群中，OS和PFS的集合危险比（HR）以及ORR的集合几率比（OR）分别为0.80、0.75和1.51；而在CPS≥10的人群中，OS和PFS的集合危险比（HR）以及ORR的集合几率比（OR）分别为0.67、0.63和1.90（所有P值均小于0.0001）。在PD-L1阴性人群中（CPS 结论：PD-L1阴性人群中，PD-L1阴性人群的PD-L2和PD-L2阳性率分别为0.67%和0.63%：本荟萃分析证实，PD-1阻断治疗在GEA患者中的获益与PD-L1 CPS有关，CPS临界值越高，获益越大，而在CPS≥10的人群中没有OS获益。

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.