Regorafenib as maintenance therapy after first-line doxorubicin-based chemotherapy in advanced non-adipocytic soft tissue sarcomas patients: a double-blind randomised trial.

IF 56.7 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2025-04-08 DOI:10.1016/j.annonc.2025.03.024

N Penel, A Italiano, J Wallet, L Chaigneau, B Verret, N Firmin, S Watson, T Valentin, E Bompas, F Bertucci, M Brahmi, C Henon, A Brunot, M Spalato-Ceruso, M Vanseymortier, E Heyman-Decoupigny, T Ryckewaert, M C Le Deley, C Perrin, J Y Blay

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引用次数: 0

Abstract

Background: There is no approved maintenance therapy in advanced non-adipocytic soft tissue sarcomas (STS). We explore here the role of regorafenib as a potential maintenance therapy after first-line treatment.

Patients and methods: EREMISS (NCT03793361) was a double-blind, placebo-controlled, comparative, 1 : 1 randomised phase II trial assessing the activity and safety of regorafenib (120 mg/day, 3 weeks on/1 week off) in patients with non-adipocytic STS, who had stable disease or partial response after six cycles of doxorubicin-based chemotherapy as first-line treatment of advanced disease. The primary endpoint was progression-free survival (PFS) according to RECIST 1.1 evaluated by blinded central review. Based on the following assumptions: PFS (placebo) = 4 months, expected PFS (regorafenib) = 7 months, hazard ratio (HR) = 0.57, one-sided α = 0.05 and β = 0.10, 110 events and 126 patients were required. This study was supported by French National Cancer Institute, a patient advocacy group and Bayer HealthCare.

Results: The study population consisted of 126 patients enrolled in 17 centres from May 2019 to November 2022. Female patients accounted for 55% of total enrolment. The median age was 58 years (range 18-85 years). The most common histological subtype was leiomyosarcoma (59%). The primary objective was assessable in 122 patients (109 events). Median PFS by blinded central review was 3.5 (placebo) versus 5.6 months (regorafenib) (HR = 0.53, 95% CI 0.36-0.78; P = 0.001). Median overall survival was 20.5 versus 27.6 months (HR = 0.78, 95% CI 0.50-1.22, P = 0.28). The proportion of patients with grade ≥3 adverse events was 4.8% (placebo) versus 56.3% (regorafenib). The most common grade ≥3 clinical adverse events in the regorafenib arm were asthenia (9%), arterial hypertension (8%), and rash (8%).

Conclusion: This trial met its primary objective, regorafenib significantly delayed disease progression after first-line treatment in advanced non-adipocytic STS. This was associated with a non-significant trend of overall survival improvement.

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瑞戈非尼作为晚期非脂肪细胞性软组织肉瘤患者一线阿霉素化疗后的维持治疗：一项双盲随机试验

背景：晚期非脂肪细胞性软组织肉瘤（STS）没有被批准的维持治疗。我们在此探讨瑞非尼作为一线治疗后潜在的维持治疗的作用。患者和方法：EREMISS （NCT03793361）是一项双盲、安慰剂对照、比较、1:1随机的II期试验，评估regorafenib （120mg /天，3周开/1周停）在非脂肪细胞性STS患者中的活性和安全性，这些患者在接受了6个周期的以阿霉素为基础的化疗作为晚期疾病的一线治疗后，病情稳定或部分缓解。主要终点是通过盲法中心回顾评估的RECIST 1.1无进展生存期（PFS）。基于以下假设：PFS（安慰剂）= 4个月，预期PFS (regorafenib) = 7个月，风险比(HR) = 0.57，单侧α = 0.05, β = 0.10，需要110个事件和126例患者。这项研究得到了法国国家癌症研究所、患者权益组织和拜耳医疗保健公司的支持。研究人群包括126名患者，于2019年5月至2022年11月在17个中心登记。女性患者占总入组人数的55%。中位年龄为58岁（18-85岁）。最常见的组织学亚型为平滑肌肉瘤（59%）。122例患者（109个事件）的主要目标可评估。盲法中心评价的中位PFS为3.5个月（安慰剂）vs 5.6个月（瑞非尼）(HR = 0.53, 95% CI 0.36-0.78；P = 0.001)。中位总生存期分别为20.5个月和27.6个月（HR = 0.78, 95% CI 0.50-1.22, P = 0.28）。≥3级不良事件的患者比例为4.8%（安慰剂组）和56.3%（瑞非尼组）。瑞非尼组最常见的≥3级临床不良事件是虚弱（9%）、动脉高血压（8%）和皮疹（8%）。结论：该试验达到了其主要目标，regorafenib在一线治疗后显著延缓了晚期非脂肪细胞性STS的疾病进展。这与总体生存改善的非显著趋势相关。

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

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.