Randomized Phase II Trial of Bevacizumab or Temsirolimus in Combination With Chemotherapy for First Relapse Rhabdomyosarcoma: A Report From the Children's Oncology Group
Randomized Phase II Trial of Bevacizumab or Temsirolimus in Combination With Chemotherapy for First Relapse Rhabdomyosarcoma: A Report From the Children's Oncology Group
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DOI：
10.1200/jco.19.00576
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发表时间：
2019-11-01
影响因子：
45.3
通讯作者：
Hawkins, Douglas S.
中科院分区：
文献类型：
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作者：
Mascarenhas, Leo;Chi, Yueh-Yun;Hawkins, Douglas S.
本临床试验的主要目的是优先考虑贝伐单抗或替西罗莫司，用于在横纹肌肉瘤（RMS）中与细胞毒性化疗联合给药时对首次复发且预后不良的RMS患者进行额外的研究。第1天和第8天联合长春瑞滨，第1天联合环磷酰胺，最多12个周期。治疗6周后，允许通过手术和/或放射治疗进行局部肿瘤控制。主要终点为无事件生存期（EFS）。在6周时评估影像学缓解。该研究有一个第二阶段的选择，旨在检测两种方案之间的差异为15%（α = 0.2; 1-β = 0.8;双侧检验）。该分析中的奥布莱恩弗莱明边界对应于双侧P值0.058，观察到的双侧P值0.003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%）和69.1%（95% CI，55.1%-83%）。客观缓解率为28%。（95% CI，13.7%至41.3%）和47%贝伐珠单抗和替西罗莫司组分别为（95% CI，31.5%-63.2%）（P = 0.12），28%接受贝伐珠单抗治疗的患者和11%结论与贝伐单抗相比，接受替西罗莫司治疗的患者具有上级EFS。已选择替西罗莫司用于新诊断的中度风险RMS患者的额外研究。
PURPOSE 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 AND METHODS 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 (alpha = .2; 1-beta = 0.8; two sided test).RESULTS 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 P value of .058 with an observed two-sided P 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 (P = .12) and, 28% of patients on bevacizumab and 11% on temsirolimus had progressive disease at 6 weeks.CONCLUSION 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.