针对局部晚期或转移性上皮样血管内皮细胞瘤患者的曲美替尼单臂2期试验

IF 10 1区 医学 Q1 ONCOLOGY Clinical Cancer Research Pub Date : 2024-10-15 DOI:10.1158/1078-0432.CCR-23-3817
Scott M Schuetze, Karla V Ballman, Rachel Heise, Kristen N Ganjoo, Elizabeth J Davis, Suzanne George, Melissa A Burgess, Edwin Choy, Dale R Shepard, Gabriel Tinoco, Angela Hirbe, Ciara M Kelly, Steven Attia, Hari A Deshpande, Gary K Schwartz, Brittany L Siontis, Richard F Riedel, Margaret von Mehren, Erin Kozlowski, Helen X Chen, Caroline Astbury, Brian P Rubin
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引用次数: 0

摘要

目的:上皮样血管内皮细胞瘤(EHE)是一种罕见的血管肿瘤,其致病因子TAZ-CAMTA1通过激活MAPK通路发挥致癌驱动作用。曲美替尼是MEK的抑制剂,MEK是MAPK通路中的一个关键激酶。我们试图评估曲美替尼对EHE患者的影响:在局部晚期或转移性 EHE 患者中开展了曲美替尼的 2 期试验。入选资格包括肿瘤进展证据或入选前存在需要阿片类药物治疗的EHE相关疼痛。主要终点是根据RECIST1.1对经融合-FISH确认的TAZ-CAMTA1病例的客观反应率(ORR)。次要目标是估计所有患者的ORR、中位PFS、2年OS率、患者安全性以及PROMIS调查问卷中患者报告的总体健康和疼痛评分变化:44名患者入组,42名患者开始接受曲美替尼治疗。27份肿瘤样本中检测到TAZ-CAMTA1。目标人群的ORR为3.7% (95% CI: 0.094, 19.0),中位PFS为10.4个月 (95% CI: 7.1, NA),2年OS率为33.3% (95% CI: 19.1, 58.2)。使用鸦片制剂的患者服用曲美替尼4周后,疼痛强度和干扰评分中位数明显改善。与曲美替尼相关的常见AE为皮疹、疲劳、恶心/呕吐、腹泻/便秘、脱发和水肿;1例5级ARDS/肺炎与曲美替尼有关:结论:曲美替尼可减轻EHE相关疼痛,中位PFS超过6个月,为晚期EHE患者提供姑息疗法,但试验未达到ORR目标。
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A Single-Arm Phase 2 Trial of Trametinib in Patients with Locally Advanced or Metastatic Epithelioid Hemangioendothelioma.

Purpose: Epithelioid hemangioendothelioma (EHE) is a rare vascular cancer with pathogenic TAZ-CAMTA1 (calmodulinbinding transcription activator 1) operating as an oncogenic driver through activation of the MAPK pathway. Trametinib is an inhibitor of MEK, a critical kinase in the MAPK pathway. We sought to evaluate the effect of trametinib in patients with EHE.

Patients and methods: A phase 2 trial of trametinib was conducted in patients with locally advanced or metastatic EHE. Eligibility requirements included evidence of tumor progression or presence of EHE-related pain requiring opiates for management before enrollment. The primary endpoint was objective response rate (ORR) as per RECIST1.1 in cases with TAZ- CAMTA1 confirmed by fusion-FISH. Secondary objectives were to estimate ORR for all patients, median progression-free survival (PFS), 2-year overall survival (OS) rate, patient safety, and change in patient-reported global health and pain scores per PROMIS questionnaires.

Results: 44 patients enrolled and 42 started trametinib. TAZ- CAMTA1 was detected in 27 tumor samples. TheORRwas 3.7%[95% confidence interval (CI), 0.094-19.0], median PFS was 10.4 months (95%CI, 7.1-NA), and 2-year OS rate was 33.3%(95%CI, 19.1-58.2) in the target population. Median pain intensity and interference scores improved significantly after 4 weeks of trametinib in patients using opiates. Common adverse events related to trametinib were rash, fatigue, nausea/vomiting, diarrhea/constipation, alopecia, and edema; one grade 5 ARDS/pneumonitis was related to trametinib.

Conclusions: Trametinib was associated with reduction in EHE-related pain and median PFS of more than 6 months, providing palliative benefit in patients with advanced EHE, but the trial did not meet the ORR goal. See related commentary by Van Tine and Haarberg, p. 4552.

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来源期刊
Clinical Cancer Research
Clinical Cancer Research 医学-肿瘤学
CiteScore
20.10
自引率
1.70%
发文量
1207
审稿时长
2.1 months
期刊介绍: Clinical Cancer Research is a journal focusing on groundbreaking research in cancer, specifically in the areas where the laboratory and the clinic intersect. Our primary interest lies in clinical trials that investigate novel treatments, accompanied by research on pharmacology, molecular alterations, and biomarkers that can predict response or resistance to these treatments. Furthermore, we prioritize laboratory and animal studies that explore new drugs and targeted agents with the potential to advance to clinical trials. We also encourage research on targetable mechanisms of cancer development, progression, and metastasis.
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