Efficacy and safety of regorafenib in patients with metastatic or locally advanced chondrosarcoma: Results of a non-comparative, randomised, double-blind, placebo controlled, multicentre phase II study
Efficacy and safety of regorafenib in patients with metastatic or locally advanced chondrosarcoma: Results of a non-comparative, randomised, double-blind, placebo controlled, multicentre phase II study
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DOI：
10.1016/j.ejca.2021.03.039
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发表时间：
2021-04-22
影响因子：
8.4
通讯作者：
Blay, Jean-Yves
中科院分区：
文献类型：
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作者：
Duffaud, Florence;Italiano, Antoine;Blay, Jean-Yves
背景：本多队列试验探讨瑞非尼治疗晚期骨源性肉瘤患者的有效性和安全性；本报告详细介绍了转移性或局部晚期软骨肉瘤（CS）患者的队列，这些患者在既往化疗后进展。患者和方法：尽管既往标准治疗进展的CS患者被随机分配（2:1）接受瑞非尼或安慰剂。在中心确诊疾病进展后，使用安慰剂的患者可以交叉使用瑞非尼。主要终点是12周时的无进展率（PFR）。单侧a为0.05，功率为80%，12周时至少需要16/24例无进展患者才能成功（P0 = 50%, P1 = 75%）。结果：2014年9月至2019年2月，46例患者纳入CS队列，40例患者可评估疗效：安慰剂组16例，瑞非尼组24例。regorafenib治疗12周时，13例患者（54.2%,95% CI[35.8%-[）无进展，安慰剂组为5例（31.3%,95% CI[13.2%-[）；)。瑞非尼组的中位PFS为19.9周，安慰剂组为8.0周。14名安慰剂患者在病情进展后转而使用瑞非尼。瑞非尼最常见的bbbb3级治疗相关不良事件包括高血压（12%）、虚弱（8%）、血小板减少（8%）和腹泻（8%）。服用瑞非尼后发生1例致死性肝功能障碍。结论：尽管在这个小型随机队列中，主要终点在统计学上没有达到，但有适度的证据表明，瑞非尼可能会减缓先前化疗失败后转移性CS患者的疾病进展。临床试验注册：该试验在ClinicalTrials.gov上注册（NCT02389244）。爱思唯尔有限公司版权所有。
Background: This multi-cohort trial explored the efficacy and safety of regorafenib for patients with advanced sarcomas of bone origin; this report details the cohort of patients with metastatic or locally advanced chondrosarcoma (CS), progressing after prior chemotherapy. Patients and methods: Patients with CS, progressing despite prior standard therapy, were randomised (2:1) to receive regorafenib or placebo. Patients on placebo could crossover to receive regorafenib after centrally confirmed progressive disease. The primary endpoint was progression-free rate (PFR) at 12 weeks. With one-sided a of 0.05, and 80% power, at least 16/24 progression-free patients at 12 weeks were needed for success (P0 = 50%, P1 = 75%). Results: From September 2014 to February 2019, 46 patients were included in the CS cohort, and 40 patients were evaluable for efficacy: 16 on placebo and 24 on regorafenib. Thirteen patients (54.2%; 95% CI [35.8%-[) were non-progressive at 12 weeks on regorafenib versus 5 (31.3%; 95% CI [13.2%-[);) on placebo. Median PFS was 19.9 weeks on regorafenib, and 8.0 on placebo. Fourteen placebo patients crossed over to regorafenib after progression. The most common grade >3 treatment-related adverse events on regorafenib included hypertension (12%), asthenia (8%), thrombocytopenia (8%) and diarrhoea (8%). One episode of fatal liver dysfunction occurred on regorafenib. Conclusion: Although the primary endpoint was not met statistically in this small randomised cohort, there is modest evidence to suggest that regorafenib might slow disease progression in patients with metastatic CS after the failure of prior chemotherapy. Clinical trial registration: The trial is registered at ClinicalTrials.gov (NCT02389244). 2021 Elsevier Ltd. All rights reserved.