在亚洲 ROS1 阳性非小细胞肺癌患者中，恩替瑞尼与克唑替尼的比较：匹配调整后的间接比较

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer Pub Date : 2024-11-10 DOI:10.1016/j.lungcan.2024.108018

Yongfeng Yu , Yun Fan , Xiaorong Dong , Juan Li , Yan Yu , Jun Zhao , Sha Tao , Yujun Chen , Mo Chen , Yueming Liu , Jiahui Xu , Qiaonan Zhu , Xichun Hu , Shun Lu

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引用次数: 0

摘要

目的：恩替利尼和克唑替尼是唯一可用于大多数亚洲患者的ROS原癌基因1受体（ROS1）酪氨酸激酶抑制剂。在 ROS1 阳性非小细胞肺癌（NSCLC）患者的临床试验中，这两种药物的疗效既没有进行过直接比较，也没有在亚洲人群中进行过间接比较。因此，我们旨在提供恩替利尼和克唑替尼对晚期或转移性ROS1阳性NSCLC亚洲患者的疗效和安全性的比较证据：采用非锚定匹配调整间接比较法（MAIC）评估疗效（包括总生存期（OS）和无进展生存期（PFS））和安全性。entrectinib试验（ALKA-372-001/EudraCT 2012-000148-88、STARTRK-1/NCT02097810和STARTRK-2/NCT02568267；剂量≥600毫克，每日一次；对克唑替尼试验（OxOnc/NCT01945021；剂量：250 毫克，每日两次）的入组截止日期为 2020 年 7 月 2 日；数据截止日期为 2021 年 8 月 2 日）和模拟伪 IPD 的汇总数据进行了分析。克唑替尼试验的主要资格标准适用于恩替瑞尼试验的IPD。采用倾向得分加权法对两组患者的基线特征进行了匹配调整：entrectinib试验和克唑替尼试验中分别有52例和127例患者可供评估。entrectinib试验组未达到中位OS（NR；加权；95%置信区间[CI] 28.3-NR），克唑替尼试验组为44.2个月（95% CI 32.0-NR）（危险比[HR]，0.662；95% CI 0.32-1.37）。中位 PFS 分别为 39.4 个月（加权；95 % CI 10.4-46.8）和 15.9 个月（95 % CI 12.9-24.0）（HR，0.688；95 % CI 0.37-1.27）。大多数 AE 为 1-2 级；两种药物的耐受性普遍良好。中性粒细胞减少是恩替替尼和克唑替尼最常见的3级或4级治疗相关不良事件：结论：这项MAIC研究包括ROS1阳性NSCLC亚裔患者，研究结果显示，恩替利尼与克唑替尼相比具有更大的临床获益趋势。这些发现可能有助于做出更明智的治疗决定。

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Entrectinib versus crizotinib in Asian patients with ROS1-positive non-small cell lung cancer: A matching-adjusted indirect comparison

Objectives

Entrectinib and crizotinib are the only ROS proto-oncogene 1 receptor (ROS1) tyrosine kinase inhibitors available for most Asian patients. Their efficacy has neither been compared directly in clinical trials in patients with ROS1-positive non-small cell lung cancer (NSCLC), nor indirectly in Asian populations. Thus, we aimed to provide comparative evidence of the efficacy and safety of entrectinib and crizotinib for Asian patients with advanced or metastatic ROS1-positive NSCLC.

Materials and Methods

Efficacy, including overall survival (OS) and progression-free survival (PFS), and safety were evaluated using an unanchored matching-adjusted indirect comparison (MAIC). Individual patient data (IPD) from entrectinib trials (ALKA-372–001/EudraCT 2012–000148-88, STARTRK-1/NCT02097810, and STARTRK-2/NCT02568267; dosage, ≥600 mg once daily; enrollment cutoff, 02 July 2020; data cutoff, 02 August 2021) and aggregate data with simulated pseudo-IPD from a crizotinib trial (OxOnc/NCT01945021; dosage, 250 mg twice daily) were analyzed. Key eligibility criteria from the crizotinib trial were applied to IPD from the entrectinib trials. Baseline characteristics were match-adjusted between arms using propensity score weighting.

Results

Fifty-two and 127 patients from the entrectinib and crizotinib trials, respectively, were available for evaluation. Median OS was not reached (NR; weighted; 95 % confidence interval [CI] 28.3–NR) in the entrectinib arm and 44.2 months (95 % CI 32.0–NR) in the crizotinib arm (hazard ratio [HR], 0.662; 95 % CI 0.32–1.37). The respective median PFS was 39.4 months (weighted; 95 % CI 10.4–46.8) and 15.9 months (95 % CI 12.9–24.0) (HR, 0.688; 95 % CI 0.37–1.27). Most AEs were Grade 1–2; both drugs were generally well tolerated. Neutropenia was the most common Grade 3 or 4 treatment-related adverse event for both entrectinib and crizotinib.

Conclusions

The outcomes in this MAIC study including Asian patients with ROS1-positive NSCLC showed a trend for greater clinical benefit with entrectinib versus crizotinib. These findings may contribute to better-informed treatment decisions.

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来源期刊

Lung Cancer 医学-呼吸系统

CiteScore

9.40

自引率

3.80%

发文量

407

审稿时长

25 days

期刊介绍： Lung Cancer is an international publication covering the clinical, translational and basic science of malignancies of the lung and chest region.Original research articles, early reports, review articles, editorials and correspondence covering the prevention, epidemiology and etiology, basic biology, pathology, clinical assessment, surgery, chemotherapy, radiotherapy, combined treatment modalities, other treatment modalities and outcomes of lung cancer are welcome.