Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy.
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands; Department of Pediatric Oncology, Emma Children's Hospital-Academic Medical Center Amsterdam, the Netherlands.
Eur J Cancer. 2020 May;130:72-80. doi: 10.1016/j.ejca.2020.01.029. Epub 2020 Mar 13.
We analysed the cohort of paediatric patients with metastatic non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) treated in the BERNIE protocol, i.e. open-label, multicentre, randomised phase II study evaluating the role of bevacizumab (BO20924/ITCC-006; ClinicalTrials.gov: NCT00643565).
Eligible patients were randomised 1:1 to add or not add bevacizumab to nine courses of intensive multi-drug chemotherapy, followed by 12-month maintenance chemotherapy (plus surgery and radiotherapy). The primary end-point was event-free survival (EFS); secondary objectives were objective response rate (ORR) and overall survival (OS).
From 2008 and 2013, 49 NRSTS patients (out of 154 cases) were treated, 26 in the standard arm and 23 in the bevacizumab arm. ORR was seen in 10 out of 36 evaluable cases (27.7%), i.e. 4/18 standard arm cases and 6/18 bevacizumab arm cases. Two-year EFS was 27.3% (95% confidence interval [CI] 13.9-42.5) for all NRSTS patients, i.e. 34.9% (95% CI 14.6-56.2) for bevacizumab arm and 22.9% (95% CI 7.1-43.9) for standard arm (p-value = 0.19). Three-year OS (median follow-up 48.6 months) was 35.2%, with no differences in the two arms. Time to event and time to death were 16.3 and 17.2 months for bevacizumab arm and 2.1 and 7.6 months for standard arm, respectively. Patients not receiving any local treatment on primary disease had a worse outcome as compared to others. Treatment results were better for patients receiving surgical resection and worse for those who did not receive any specific treatment.
The addition of the anti-angiogenic agent to the standard chemotherapy did not show statistically significant improvement in survival in metastatic NRSTS.
我们分析了 BERNIE 方案治疗的转移性非横纹肌肉瘤软组织肉瘤（NRSTS）儿科患者队列，即开放标签、多中心、随机 II 期研究，评估贝伐单抗（BO20924/ITCC-006；ClinicalTrials.gov：NCT00643565）的作用。
符合条件的患者按 1:1 随机分配，接受或不接受贝伐单抗联合 9 个疗程的强化多药化疗，然后接受 12 个月的维持化疗（加手术和放疗）。主要终点是无事件生存（EFS）；次要目标是客观缓解率（ORR）和总生存（OS）。
2008 年至 2013 年，49 例 NRSTS 患者（154 例中的 49 例）接受治疗，标准组 26 例，贝伐单抗组 23 例。36 例可评估病例中有 10 例（27.7%）出现客观缓解，即标准组 4 例，贝伐单抗组 6 例。所有 NRSTS 患者的 2 年 EFS 为 27.3%（95%置信区间 [CI] 13.9-42.5），贝伐单抗组为 34.9%（95% CI 14.6-56.2），标准组为 22.9%（95% CI 7.1-43.9）（p 值=0.19）。3 年 OS（中位随访 48.6 个月）为 35.2%，两组间无差异。贝伐单抗组的时间事件和死亡时间分别为 16.3 个月和 17.2 个月，标准组分别为 2.1 个月和 7.6 个月。初发病灶未接受任何局部治疗的患者预后较差。接受手术切除的患者治疗效果较好，未接受任何特定治疗的患者治疗效果较差。
抗血管生成药物联合标准化疗在转移性 NRSTS 患者的生存中未显示出统计学显著改善。
