Dinutuximab Beta Added to Temozolomide-Based Chemotherapy for Children With Relapsed and Refractory Neuroblastoma: Results of the ITCC-SIOPEN BEACON Immuno Phase II Trial.

materials_and_methods

Patients with RR-HR-NBL were randomly assigned in a 1:2 ratio to receive chemotherapy alone or chemotherapy with dB, given concurrently as a 7-day infusion (10 mg/m2/24 h).

RR-HR-NBL患者按1:2的比例随机分配接受单独化疗或与dB同时给药的化疗，后者以7天的输注方式给予（10 mg/m2/24 h）。

The trial had a factorial design, with some patients also randomly assigned between chemotherapy regimens (T v T-topotecan [TTo]).

该试验采用析因设计，部分患者在化疗方案（T与T-topotecan [TTo]）之间进行随机分配。

Crossover to dB with To/cyclophosphamide was allowed for patients randomly assigned to chemotherapy alone with disease progression (PD).

对于仅接受化疗且疾病进展（PD）的随机分配患者，允许转为dB与To/环磷酰胺治疗。

The primary outcome was best objective response (complete or partial) rate (overall response rate [ORR]) during six cycles of treatment.

主要结果是在六个治疗周期内最佳客观反应（完全或部分）率（总反应率[ORR]）。

Progression-free (PFS), overall survival(OS), and safety were secondary outcomes.

无进展生存（PFS）、总生存（OS）和安全性是次要结果。

Results

Sixty-five patients were randomly assigned to chemotherapy alone (3 T, 19 TTo) or with dB (6 dBT, 37 dBTTo).

65名患者被随机分配接受单纯化疗（3 T，19 TTo）或联合dB治疗（6 dBT，37 dBTTo）。

The median age was 4 years; 28 and 37 patients had refractory and relapsed diseases, respectively.

中位年龄为4岁；分别有28名和37名患者患有难治性和复发性疾病。

Baseline characteristics were balanced between arms.

两组基线特征均衡。

The ORR was 30.2% (13 of 43) and 18.2% (4 of 22) in dB and non-dB arms, the median PFS was 11.1 months (95% CI, 4.3 to 15.5) for dB patients and 3.8 months (95% CI, 1.9 to 7.9) for non-dB patients, respectively.

客观缓解率（ORR）在dB组和非dB组分别为30.2%（43人中有13人）和18.2%（22人中有4人），dB患者的中位无进展生存期（PFS）为11.1个月（95%置信区间，4.3至15.5个月），非dB患者为3.8个月（95%置信区间，1.9至7.9个月）。

The median OS was 25.7 months (95% CI, 11.4 to not reached [NR]) for dB patients and 17.1 months (95% CI, 7.6 to 54.6) for non-dB patients (upper 95% CI, NR in dB arm).

对于dB患者的中位总生存期为25.7个月（95%置信区间，11.4至未达到[NR]），而对于非dB患者的中位总生存期为17.1个月（95%置信区间，7.6至54.6）（dB组的上限95%置信区间，未达到）。

Thirteen of 22 patients in the non-dB arm crossed over to dB with cyclophosphamide/To because of PD.

在非dB组的22名患者中，有13名因疾病进展（PD）转为接受环磷酰胺/To治疗的dB组。

Neurotoxicity was more common in the dB arm (grade 1 and 2: 26% v 9%, grade 3: 2.3% v 4.5%), but other toxicities were similar.

在 dB 组中，神经毒性更为常见（1级和2级：26% 对比 9%，3级：2.3% 对比 4.5%），但其他毒性相似。

Conclusions

Within a randomized phase II setting, results observed with addition of dB to T-based chemotherapy in RR-HR-NB warrant further evaluation.

在随机化的II期临床试验中，将 dB 添加到以 T 为基础的化疗方案中，在复发高危神经母细胞瘤（RR-HR-NB）中的结果值得进一步评估。