Anlotinib versus Placebo as Adjuvant Therapy for Localized High-Grade Soft-Tissue Sarcomas: A Phase II, Double-Blinded, Randomized Controlled Trial.

patients_and_methods

Patients with localized high-grade STS after complete resection were randomly assigned in a 1:1 ratio to receive either oral 12 mg anlotinib or placebo once daily on days 1 to 14 every 21 days as a cycle, with up to six cycles until disease relapse, unmanageable toxicity, or death.

完全切除局部高级别STS的患者按1:1的比例随机分配，接受口服12毫克阿帕替尼或安慰剂，每天一次，第1天至第14天为一个周期，每21天一个周期，最多六个周期，直到疾病复发、无法管理的毒性或死亡。

The efficacy and safety were analyzed.

分析了疗效和安全性。

This trial was the first trial exploring adjuvant targeted therapy for STS (NCT03951571).

本试验是首个探索软组织肉瘤辅助靶向治疗的试验（NCT03951571）。

Results

Between June 2019 and November 2023, 88 patients were randomly assigned to receive anlotinib (n = 44) or placebo (n = 44).

在2019年6月至2023年11月期间，88名患者被随机分配接受阿洛替尼（n = 44）或安慰剂（n = 44）。

With a median follow-up of 30.95 months, the 1- and 2-year disease-free survival rates were 88% and 77% in the anlotinib group compared with 64% and 58% in the placebo group, respectively.

中位随访时间为30.95个月，阿洛替尼组1年和2年的无病生存率分别为88%和77%，而安慰剂组则分别为64%和58%。

Compared with patients treated with surgery alone, patients receiving adjuvant anlotinib combined with surgery had a reduced risk of disease recurrence [HR, 0.47; 95% confidence interval(CI), 0.22-1.00; P = 0.0445].

与仅接受手术治疗的患者相比，接受辅助性安罗替尼联合手术治疗的患者疾病复发风险降低[风险比（HR），0.47；95%置信区间（CI），0.22-1.00；P = 0.0445]。

Based on the tumor histology, the reduced risk of disease recurrence with anlotinib versus placebo was observed in patients with myxofibrosarcoma (HR, 0.54; 95% CI, 0.17-1.65; P = 0.2698) and undifferentiated pleomorphic sarcoma (HR, 0.58; 95% CI, 0.12-2.87; P = 0.4971).

根据肿瘤组织学，与安慰剂相比，安罗替尼在降低粘液纤维肉瘤患者（HR，0.54；95% CI，0.17-1.65；P = 0.2698）和未分化多形性肉瘤患者（HR，0.58；95% CI，0.12-2.87；P = 0.4971）的疾病复发风险方面显示出效果。

Four patients discontinued anlotinib: two for proteinuria/hematuria (2/44, 5%) and two for poor healing of surgical wound (2/44, 5%).

四名患者停止使用阿乐替尼：两名因蛋白尿/血尿（2/44，5%），另外两名因手术伤口愈合不良（2/44，5%）。

Conclusions

Compared with surgery alone, adjuvant anlotinib following surgery reduces the incidenceof disease relapse in localized high-grade STS, with acceptable toxicity.

与单纯手术相比，手术后辅助使用阿乐替尼可降低局部高级别软组织肉瘤疾病复发的发生率，且毒性可接受。