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

We explore here the role of regorafenib as a potential maintenance therapy after first-line treatment.

我们在这里探讨了瑞戈非尼作为一线治疗后潜在维持治疗方案的作用。

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.

EREMISS (NCT03793361) 是一项双盲、安慰剂对照、比较性的1:1随机II期试验，评估了在首次治疗晚期非脂肪肉瘤患者中，经过六周期多柔比星化疗后疾病稳定或部分缓解的患者，每日120毫克的瑞戈非尼（3周用药/1周停药）的疗效和安全性。

The primary endpoint was progression-free survival(PFS) according to RECIST 1.1 evaluated by blinded central review.

主要终点是根据RECIST 1.1标准由盲法中心审查评估的无进展生存期（PFS）。

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.

基于以下假设：无进展生存期（安慰剂组）= 4个月，预期无进展生存期（瑞戈非尼组）= 7个月，风险比（HR）= 0.57，单侧α = 0.05和β = 0.10，需要110个事件和126名患者。

This study was supported by French National Cancer Institute, a patient advocacy group and Bayer HealthCare.

这项研究得到了法国国家癌症研究所、一个患者倡导组织和拜耳健康护理的支持。

Results

The study population consisted of 126 patients enrolled in 17 centres from May 2019 to November 2022.

研究人群包括2019年5月至2022年11月期间在17个中心登记的126名患者。

Female patients accounted for 55% of total enrolment.

女性患者占总登记人数的55%。

The median age was 58 years (range 18-85 years).

中位年龄为58岁（范围18-85岁）。

The most common histological subtype was leiomyosarcoma (59%).

最常见的组织学亚型是平滑肌肉瘤（占59%）。

The primary objective was assessable in 122 patients (109 events).

主要研究终点在122名患者中是可评估的（109个事件）。

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).

通过盲法中心审查得出的中位无进展生存期为3.5个月（安慰剂组）对比5.6个月（瑞戈非尼组）（HR=0.53，95% 置信区间 0.36-0.78；P=0.001）。

Median overall survivalwas 20.5 versus 27.6 months (HR = 0.78, 95% CI 0.50-1.22, P = 0.28).

中位总生存期为20.5个月对比27.6个月（HR=0.78，95%置信区间0.50-1.22，P=0.28）。

The proportion of patients with grade ≥3 adverse events was 4.8% (placebo) versus 56.3% (regorafenib).

≥3级不良事件的发生比例为4.8%（安慰剂组）对比56.3%（瑞戈非尼组）。

The most common grade ≥3 clinical adverse events in the regorafenib arm were asthenia (9%), arterial hypertension (8%), and rash (8%).

在瑞戈非尼组中，最常见的3级或以上临床不良事件是乏力（9%）、动脉高血压（8%）和皮疹（8%）。

Conclusions

This trial met its primary objective, regorafenib significantly delayed disease progression after first-line treatment in advanced non-adipocytic STS.

这项试验达到了其主要目标，瑞戈非尼显著延迟了晚期非脂肪肉瘤患者一线治疗后的疾病进展。

This was associated with a non-significant trend of overall survivalimprovement.

这与总生存期改善的非显著趋势相关。