Randomized Phase II Trial of Vincristine-Irinotecan With or Without Temozolomide, in Children and Adults With Relapsed or Refractory Rhabdomyosarcoma: A European Paediatric Soft Tissue Sarcoma Study Group and Innovative Therapies for Children With Cancer Trial
Randomized Phase II Trial of Vincristine-Irinotecan With or Without Temozolomide, in Children and Adults With Relapsed or Refractory Rhabdomyosarcoma: A European Paediatric Soft Tissue Sarcoma Study Group and Innovative Therapies for Children With Cancer Trial
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DOI：
10.1200/jco.21.00124
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发表时间：
2021-09-20
影响因子：
45.3
通讯作者：
Chisholm, Julia C.
中科院分区：
文献类型：
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作者：
Defachelles, Anne-Sophie;Bogart, Emilie;Chisholm, Julia C.
目的 VIT-0910 试验旨在评估长春新碱-伊立替康组合联合或不联合替莫唑胺（分别为 VIT 和 VI）治疗复发或难治性横纹肌肉瘤 (RMS) 的疗效和安全性。方法 在这项随机欧洲 II 期试验中，年龄 0.5-50 岁的患者接受为期 21 天的周期，联合使用长春新碱（1.5 mg/m(2)，第 1 天和第 8 天每天一次）和伊立替康（50 mg/m(2)，第 1 天到第 5 天每天一次），联合或不联合替莫唑胺（125 mg/m(2)，第 1 天到第 5 天每天一次，以及第 150 天） mg/m(2) 每天一次，从 周期2)，直到进展或出现不可接受的毒性。主要终点是两个周期后的客观缓解率。次要终点包括最佳反应、无进展生存期、总生存期和不良事件。 Simon 2 阶段设计最初计划分别分析每组 40 名患者。修改后，试验样本量增加到 120 个，并在统计计划中添加了根据混杂因素进行调整的组间比较（ClinicalTrials.gov，）。结果 总体而言，在 37 个欧洲中心招募了 120 名患者（每组 60 名）。中位年龄为 11 岁（范围为 0.75-45）； 89% 的患者患有复发性 RMS。 VIT 的客观缓解率为 44%（55 名可评估患者中的 24 名），而 VI 的客观缓解率为 31%（58 名可评估患者中的 18 名）（调整后优势比，0.50；95% CI，0.22 至 1.12；P = .09）。与 VI 相比，VIT 组的总体生存率显着提高（调整后风险比，0.55；95% CI，0.35 至 0.84；P = .006），并且无进展生存结果一致（调整后风险比，0.68；95% CI，0.46 至 1.01；P = .059）。总体而言，VIT 患者比 VI 患者更频繁地经历 3 级以上不良事件（分别为 98% 对 78%；P = .009），包括显着过量的血液学毒性（81% 对 61%；P = .025）。结论 VI 中添加替莫唑胺可改善复发 RMS 患者的化疗疗效，同时毒性增加可控。 VIT 被认为是欧洲儿科软组织肉瘤组这些患者的新标准治疗方法，并将成为下一个随机试验的对照组。
PURPOSE The VIT-0910 trial was conducted to evaluate efficacy and safety of the vincristine-irinotecan combination with and without temozolomide (VIT and VI, respectively) in relapsed or refractory rhabdomyosarcoma (RMS). METHODS In this randomized European phase II trial, patients age 0.5-50 years received 21-day cycles combining vincristine (1.5 mg/m(2) once a day on day 1 and day 8) and irinotecan (50 mg/m(2) once a day from day 1 to day 5) with and without temozolomide (125 mg/m(2) once a day from day 1 to day 5 and 150 mg/m(2) once a day from cycle 2), until progression or unacceptable toxicity. The primary end point was objective response rate after two cycles. Secondary end points included best response, progression-free survival, overall survival, and adverse events. A Simon 2-stage design was initially planned to separately analyze 40 patients/arm. After amendment, the trial sample size was increased to 120 and a comparison between arms, adjusted for confounding factors, was added to the statistical plan (ClinicalTrials.gov, ). RESULTS Overall, 120 patients (60 per arm) were recruited in 37 European centers. The median age was 11 years (range, 0.75-45); 89% of patients had a relapsed RMS. The objective response rate was 44% (24 of 55 evaluable patients) for VIT versus 31% (18 of 58) for VI (adjusted odds ratio, 0.50; 95% CI, 0.22 to 1.12; P = .09). The VIT arm achieved significantly better overall survival (adjusted hazard ratio, 0.55; 95% CI, 0.35 to 0.84; P = .006) compared with VI, with consistent progression-free survival results (adj-hazard ratio, 0.68; 95% CI, 0.46 to 1.01; P = .059). Overall, patients experienced adverse events >= grade 3 more frequently with VIT than VI (98% v 78%, respectively; P = .009), including a significant excess of hematologic toxicity (81% v 61%; P = .025). CONCLUSION The addition of temozolomide to VI improved chemotherapy efficacy for patients with relapsed RMS, with manageable increase in toxicity. VIT is considered the new standard treatment in these patients in the European paediatric Soft Tissue Sarcoma Group and will be the control arm in the next randomized trial.