检测儿童低级别胶质瘤中的BRAF V600E突变与标准化疗的响应较低有关。在以往的试验中，达布来替尼（作为单独治疗和与曲墨替尼联合）在带有BRAF V600突变的复发性儿童低级别胶质瘤中显示出疗效，这些发现有待进一步评估该联合治疗作为一线治疗的效果。在本第二期试验中，计划接受一线治疗的带有BRAF V600突变的儿童低级别胶质瘤患者以2:1的比例随机分配接受达布来替尼加曲墨替尼或标准化疗（卡铂加长春新碱）。主要结果是根据神经肿瘤反应评估标准独立评估的总体反应（完全或部分反应）。此外，还评估了临床益处（完全或部分反应或稳定疾病≥24周）和无进展生存期。共有110名患者随机分组（73名接受达布来替尼加曲墨替尼治疗，37名接受标准化疗）。在中位随访时间为18.9个月时，接受达布来替尼加曲墨替尼治疗的患者中有47%出现总体反应，而接受化疗的患者中仅有11%出现总体反应（风险比为4.31；95%置信区间[CI]，1.7至11.2；P<0.001）。86%的接受达布来替尼加曲墨替尼治疗的患者获得临床益处，而接受化疗的患者中有46%（风险比，1.88；95% CI，1.3至2.7）。达布来替尼加曲墨替尼的中位无进展生存期显著长于化疗（20.1个月对7.4个月；风险比为0.31；95% CI，0.17至0.55；P<0.001）。接受达布来替尼加曲墨替尼治疗的患者中发生3级或更高级别的不良事件的比例为47%，而接受化疗的患者中为94%。在BRAF V600突变的儿童低级别胶质瘤患者中，达布来替尼加曲墨替尼比标准化疗作为一线治疗具有显著更多的反应、更长的无进展生存期和更好的安全性。 (由诺华公司赞助; ClinicalTrials.gov编号, NCT02684058)。版权所有 © 2023 Massachusetts Medical Society.

Detection of the BRAF V600E mutation in pediatric low-grade glioma has been associated with a lower response to standard chemotherapy. In previous trials, dabrafenib (both as monotherapy and in combination with trametinib) has shown efficacy in recurrent pediatric low-grade glioma with BRAF V600 mutations, findings that warrant further evaluation of this combination as first-line therapy.In this phase 2 trial, patients with pediatric low-grade glioma with BRAF V600 mutations who were scheduled to receive first-line therapy were randomly assigned in a 2:1 ratio to receive dabrafenib plus trametinib or standard chemotherapy (carboplatin plus vincristine). The primary outcome was the independently assessed overall response (complete or partial response) according to the Response Assessment in Neuro-Oncology criteria. Also assessed were the clinical benefit (complete or partial response or stable disease for ≥24 weeks) and progression-free survival.A total of 110 patients underwent randomization (73 to receive dabrafenib plus trametinib and 37 to receive standard chemotherapy). At a median follow-up of 18.9 months, an overall response occurred in 47% of the patients treated with dabrafenib plus trametinib and in 11% of those treated with chemotherapy (risk ratio, 4.31; 95% confidence interval [CI], 1.7 to 11.2; P<0.001). Clinical benefit was observed in 86% of the patients receiving dabrafenib plus trametinib and in 46% receiving chemotherapy (risk ratio, 1.88; 95% CI, 1.3 to 2.7). The median progression-free survival was significantly longer with dabrafenib plus trametinib than with chemotherapy (20.1 months vs. 7.4 months; hazard ratio, 0.31; 95% CI, 0.17 to 0.55; P<0.001). Grade 3 or higher adverse events occurred in 47% of the patients receiving dabrafenib plus trametinib and in 94% of those receiving chemotherapy.Among pediatric patients with low-grade glioma with BRAF V600 mutations, dabrafenib plus trametinib resulted in significantly more responses, longer progression-free survival, and a better safety profile than standard chemotherapy as first-line therapy. (Funded by Novartis; ClinicalTrials.gov number, NCT02684058.).Copyright © 2023 Massachusetts Medical Society.