Utility of assessing early tumor shrinkage as an efficacy predictor in patients with non-surgically indicated or recurrent esophageal cancer treated with nivolumab plus ipilimumab.

IF 2.5 3区医学 Q3 ONCOLOGY Oncology Pub Date : 2024-08-29 DOI:10.1159/000540851

Seiji Natsuki, Shigeru Lee, Hiroaki Kasashima, Yuichiro Miki, Tatsunari Fukuoka, Mami Yoshii, Tatsuro Tamura, Masatsune Shibutani, Takahiro Toyokawa, Hiroaki Tanaka, Kiyoshi Maeda

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引用次数: 0

Abstract

Introduction: Nivolumab plus ipilimumab combination therapy has been administered as a first-line treatment in Japan since 2022 for patients with unresectable progressive or recurrent esophageal cancer. The efficacy and safety of this immune checkpoint inhibitor (ICI) doublet therapy is now being evaluated, and it is necessary to identify populations that benefit from this treatment at an early phase after initiation. For patients not showing early benefit, changing as soon as possible to other therapeutic strategies could improve their survival outcomes. Therefore, we attempted to identify decision-making factors such as early tumor shrinkage (ETS) based on treatment experience with ICI doublet therapy.

Methods: The study included 19 patients who received nivolumab plus ipilimumab for non-surgically indicated or recurrent esophageal cancer between July 2022 and November 2023. Tumors were assessed approximately every 2 months after treatment initiation. The effects of ETS, depth of response (DpR), and clinicopathologic features, including immune-related adverse events (irAEs), on progression-free and overall survival were evaluated using Kaplan-Meyer plots and Cox proportional hazard models.

Results: The mean duration of ICI doublet administration was 5.89 months (range, 1-16 months). At first evaluation, patients who exhibited no tumor progression >20% indicated possible response to ICI doublet therapy, and patients whose tumors shrank even minimally exhibited favorable progression-free survival. Higher DpR at any cut-off line exhibited better progression-free survival than those with lower DpR. Fifteen patients experienced irAEs, with 13 of these patients experiencing irAEs within 3 months of treatment initiation. irAEs were associated with the efficacy of ICI doublet therapy, but efficacy could not be predicted based on early irAE experience.

Conclusion: ETS-high, DpR-high, and irAEs might be associated with favorable responses to nivolumab plus ipilimumab. As a predictor of efficacy at an early phase, ETS >0% could be a deciding factor for continuing ICI doublet therapy.

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评估早期肿瘤缩小作为非手术指征或复发性食管癌患者接受 nivolumab 加 ipilimumab 治疗的疗效预测指标的效用。

简介自2022年起，Nivolumab加伊匹单抗联合疗法已在日本作为一线疗法用于治疗不可切除的进展期或复发性食管癌患者。目前正在对这种免疫检查点抑制剂（ICI）双联疗法的疗效和安全性进行评估，有必要在开始治疗后的早期阶段确定从这种疗法中获益的人群。对于未显示出早期获益的患者，尽快改用其他治疗策略可改善他们的生存结果。因此，我们试图根据 ICI 双联疗法的治疗经验，确定早期肿瘤缩小（ETS）等决策因素：研究纳入了2022年7月至2023年11月期间接受nivolumab加伊匹单抗治疗非手术指征或复发性食管癌的19名患者。治疗开始后，大约每两个月对肿瘤进行一次评估。使用Kaplan-Meyer图和Cox比例危险模型评估了ETS、反应深度（DpR）和临床病理特征（包括免疫相关不良事件（irAEs））对无进展生存期和总生存期的影响：ICI 双联用药的平均持续时间为 5.89 个月（1-16 个月）。首次评估时，肿瘤无进展的患者占20%，这表明患者可能对ICI双联疗法有反应，而肿瘤即使有轻微缩小的患者也能获得良好的无进展生存期。在任何截断线下，DpR较高的患者的无进展生存期均优于DpR较低的患者。15名患者出现了虹膜不良反应，其中13名患者在开始治疗后3个月内出现了虹膜不良反应。虹膜不良反应与ICI双联疗法的疗效有关，但不能根据早期的虹膜不良反应预测疗效：结论：ETS高、DpR高和irAEs可能与nivolumab加伊匹单抗的良好反应有关。作为早期疗效的预测指标，ETS>0%可能是继续使用ICI双联疗法的决定性因素。

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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来源期刊

Oncology 医学-肿瘤学

CiteScore

6.00

自引率

2.90%

发文量

审稿时长

6-12 weeks

期刊介绍： Although laboratory and clinical cancer research need to be closely linked, observations at the basic level often remain removed from medical applications. This journal works to accelerate the translation of experimental results into the clinic, and back again into the laboratory for further investigation. The fundamental purpose of this effort is to advance clinically-relevant knowledge of cancer, and improve the outcome of prevention, diagnosis and treatment of malignant disease. The journal publishes significant clinical studies from cancer programs around the world, along with important translational laboratory findings, mini-reviews (invited and submitted) and in-depth discussions of evolving and controversial topics in the oncology arena. A unique feature of the journal is a new section which focuses on rapid peer-review and subsequent publication of short reports of phase 1 and phase 2 clinical cancer trials, with a goal of insuring that high-quality clinical cancer research quickly enters the public domain, regardless of the trial’s ultimate conclusions regarding efficacy or toxicity.