晚期胃食管腺癌的免疫检查点抑制剂：不同程序性死亡配体1亚组的一系列患者水平荟萃分析。

IF 7.1 2区医学 Q1 ONCOLOGY

ESMO Open Pub Date : 2024-10-18 DOI:10.1016/j.esmoop.2024.103962

A.G. Leone , A.S. Mai , K.Y. Fong , D.W.T. Yap , K. Kato , E. Smyth , M. Moehler , J.T.C. Seong , R. Sundar , J.J. Zhao , F. Pietrantonio

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引用次数: 0

摘要

背景：虽然免疫检查点抑制剂（ICI）在程序性死亡配体1高（PD-L1高）晚期胃食管腺癌（GEAC）中的获益已得到公认，但在PD-L1低GEAC中的获益仍存在很大争议。为了阐明 ICI 对 PD-L1 低和 PD-L1 阴性 GEAC 的益处，我们利用从关键试验的 Kaplan-Meier (KM) 图中提取的患者个体数据 (IPD) 进行了分析：从发表的文章中提取了研究 ICI 对晚期 GEAC 疗效的随机临床试验的 KM 曲线。从报告的曲线中提取IPD，对于未报告的KM图，则使用KMSubtraction来检索生存数据。对PD-L1低的肿瘤进行了患者层面的荟萃分析：在人表皮生长因子受体 2 (HER2) 阴性的情况下，来自 KEYNOTE-859、CHECKMATE-649 和 RATIONALE-305 的 PD-L1 合并阳性评分 (CPS) 1-4 亚组 KM 图显示，添加抗程序性细胞死亡蛋白 1 (anti-PD-1) 药物后，总生存期 (OS) 略有获益 [危险比 (HR) 0.868，P = 0.018]。同样，我们对来自 KEYNOTE-859、KEYNOTE-062 和 RATIONALE-305 的 PD-L1 CPS 1-9 亚组进行的 IPD 荟萃分析也显示了适度的 OS 益处（HR 0.840，P = 0.002）。相反，将KEYNOTE-859和RATIONALE-305的CPS 5-9亚组KM图汇总后发现，ICI化疗组没有显著的OS获益（HR 0.867，P = 0.181），尽管该亚组相对较小：在PD-L1低HER-2阴性的GEAC中，一线ICI的获益不大，但意义重大。有必要开展进一步的转化工作，以更好地选择在这种情况下能从免疫疗法中获益的患者。与此同时，还必须考虑其他治疗方案，如用于Claudin18.2阳性疾病的唑贝妥昔单抗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Immune checkpoint inhibitors in advanced gastroesophageal adenocarcinoma: a series of patient-level meta-analyses in different programmed death-ligand 1 subgroups

Background

While the benefit of immune checkpoint inhibitors (ICI) is well established in programmed death-ligand 1 high (PD-L1_high) advanced gastroesophageal adenocarcinoma (GEAC), there remains significant controversy about their benefit in PD-L1_low GEAC. To elucidate the benefit of ICI in PD-L1_low and PD-L1_negative GEAC, we conducted an analysis leveraging individual patient data (IPD) extracted from Kaplan–Meier (KM) plots of pivotal trials.

Methods

KM curves from randomized clinical trials investigating the efficacy of ICI for advanced GEAC were extracted from published articles. IPD were extracted from the reported curves, and, in the case of unreported KM plots, KMSubtraction was used to retrieve survival data. A patient-level meta-analysis was conducted for PD-L1_low tumors.

Results

In the human epidermal growth factor receptor 2 (HER2)-negative setting, pooled PD-L1 combined positive score (CPS) 1-4 subgroup KM plots from KEYNOTE-859, CHECKMATE-649, and RATIONALE-305 showed a modest overall survival (OS) benefit with the addition of an anti-programmed cell death protein 1 (anti-PD-1) agent [hazard ratio (HR) 0.868, P = 0.018]. Similarly, a modest OS benefit was shown by our IPD meta-analysis of PD-L1 CPS 1-9 subgroups from KEYNOTE-859, KEYNOTE-062, and RATIONALE-305 (HR 0.840, P = 0.002.) Conversely, when CPS 5-9 subgroup KM plots from KEYNOTE-859 and RATIONALE-305 were pooled together, no significant OS benefit was found in the ICI-chemotherapy arm (HR 0.867, P = 0.181), although this subgroup was relatively small.

Conclusions

In PD-L1_low HER-2 negative GEAC, the benefit of first-line ICI is modest, yet significant. Further translational work is warranted to better select patients who could benefit from immunotherapy in this setting. Meanwhile, alternative therapeutic options such as zolbetuximab in Claudin18.2-positive disease must be taken into account.

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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.