Children's Hospital Los Angeles and University of Southern California Keck School of Medicine, Los Angeles, CA.
University of Florida, Gainesville, FL.
J Clin Oncol. 2019 Nov 1;37(31):2866-2874. doi: 10.1200/JCO.19.00576. Epub 2019 Sep 12.
The primary aim of this clinical trial was to prioritize bevacizumab or temsirolimus for additional investigation in rhabdomyosarcoma (RMS) when administered in combination with cytotoxic chemotherapy to patients with RMS in first relapse with unfavorable prognosis.
Patients were randomly assigned to receive bevacizumab on day 1 or temsirolimus on days 1, 8, and 15 of each 21-day treatment cycle, together with vinorelbine on days 1 and 8, and cyclophosphamide on day 1 for a maximum of 12 cycles. Local tumor control with surgery and/or radiation therapy was permitted after 6 weeks of treatment. The primary end point was event-free survival (EFS). Radiographic response was assessed at 6 weeks. The study had a phase II selection that was design to detect a 15% difference between the two regimens (α = .2; 1-β = 0.8; two sided test).
Eighty-seven of 100 planned patients were enrolled when the trial was closed after the second interim analysis after 46 events occurred in 68 patients with sufficient follow-up. The O'Brien Fleming boundary at this analysis corresponded to a two-sided value of .058 with an observed two-sided value of .003 favoring temsirolimus. The 6-month EFS for the bevacizumab arm was 54.6% (95% CI, 39.8% to 69.3%) and 69.1% (95% CI, 55.1% to 83%) for the temsirolimus arm. Objective response rates were 28% (95% CI, 13.7% to 41.3%) and 47% (95% CI, 31.5% to 63.2%) for the bevacizumab and temsirolimus arms, respectively ( = .12) and, 28% of patients on bevacizumab and 11% on temsirolimus had progressive disease at 6 weeks.
Patients who received temsirolimus had a superior EFS compared with bevacizumab. Temsirolimus has been selected for additional investigation in newly diagnosed patients with intermediate-risk RMS.
本临床试验的主要目的是在具有不良预后的首次复发的横纹肌肉瘤（RMS）患者中，当联合细胞毒性化疗时，将贝伐珠单抗或替西罗莫司优先用于另外的研究，以用于 RMS 治疗。
患者随机分配至贝伐珠单抗组（第 1 天）或替西罗莫司组（第 1、8 和 15 天），每组患者均接受每 21 天周期中的长春瑞滨（第 1 和 8 天）和环磷酰胺（第 1 天）治疗，最多治疗 12 个周期。在治疗 6 周后，允许采用手术和/或放射治疗进行局部肿瘤控制。主要终点是无事件生存（EFS）。在 6 周时评估影像学反应。该研究具有 2 期选择设计，旨在检测两种方案之间 15%的差异（α =.2；1-β = 0.8；双侧检验）。
当试验在第二次中期分析后因 68 例患者中有 46 例发生足够随访的事件而关闭时，计划入组的 100 例患者中的 87 例被入组。该分析时的 O'Brien Fleming 边界对应于双侧.058 的值，观察到双侧.003 的值有利于替西罗莫司。贝伐珠单抗组的 6 个月 EFS 为 54.6%（95%CI，39.8%至 69.3%），替西罗莫司组为 69.1%（95%CI，55.1%至 83%）。贝伐珠单抗组和替西罗莫司组的客观缓解率分别为 28%（95%CI，13.7%至 41.3%）和 47%（95%CI，31.5%至 63.2%）（ =.12），贝伐珠单抗组有 28%的患者和替西罗莫司组有 11%的患者在 6 周时出现疾病进展。
与贝伐珠单抗相比，接受替西罗莫司治疗的患者具有更好的 EFS。替西罗莫司已被选为新诊断的中危 RMS 患者的进一步研究药物。
