METHODS: Patients had localized high-grade (cellular component >5%; size ≥5 cm; deeply seated) MLPS of extremities or trunk wall. The primary end point was disease-free survival (DFS). The secondary end point was overall survival (OS). The trial used a noninferiority Bayesian design, wherein HT would be considered not inferior to S if the posterior probability of the true hazard ratio (HR) being >1.25 was <5%.
RESULTS: From May 2011 to June 2020, 101 patients with HG-MLPS were randomly assigned, 45 to the HT arm and 56 to the S arm. The median follow-up was 66 months (IQR, 37-89). Median size was 107 mm (IQR, 84-143), 106 mm (IQR, 75-135) in the HT arm and 108 mm (IQR, 86-150) in the S arm. At 60 months, the DFS and OS probabilities were 0.86 and 0.73 (HR, 0.60 [95% CI, 0.24 to 1.46]; log-rank P = .26 for DFS) and 0.88 and 0.90 (HR, 1.20 [95% CI, 0.37 to 3.93]; log-rank P = .77 for OS) in the HT and S arms, respectively. The posterior probability of HR being >1.25 for DFS met the Bayesian monitoring cutoff of <5% (4.93%). This result confirmed the noninferiority of trabectedin to AI suggested in the original study cohort.
CONCLUSIONS: Trabectedin may be an alternative to standard AI in HG-MLPS of the extremities or trunk when neoadjuvant treatment is a consideration.
方法:患者四肢或躯干壁的局部高度MLPS(细胞成分>5%;大小≥5厘米;深坐姿)。主要终点是无病生存期(DFS)。次要终点是总生存期(OS)。试验采用了非劣效性贝叶斯设计,其中,如果真实风险比(HR)>1.25的后验概率<5%,则认为HT不低于S。
结果:从2011年5月至2020年6月,101例HG-MLPS患者被随机分配,45到HT臂和56到S臂。中位随访时间为66个月(IQR,37-89)。中值尺寸为107毫米(IQR,84-143),106mm(IQR,75-135)在HT臂和108毫米(IQR,86-150)在S臂中。60个月时,DFS和OS概率分别为0.86和0.73(HR,0.60[95%CI,0.24至1.46];DFS的对数秩P=0.26)和0.88和0.90(HR,1.20[95%CI,0.37至3.93];OS的对数秩P=0.77)在HT和S臂中,分别。对于DFS,HR>1.25的后验概率满足<5%(4.93%)的贝叶斯监测截止值。该结果证实了原始研究队列中提出的trabectedin对AI的非劣效性。
结论:当考虑新辅助治疗时,在四肢或躯干的HG-MLPS中,Trabectedin可能是标准AI的替代品。