司美替尼治疗1型神经纤维瘤病和丛状神经纤维瘤儿科患者：SPRINT研究与自然病史对照臂的倾向评分分析
Selumetinib in pediatric patients with neurofibromatosis type 1 and plexiform neurofibroma: Propensity score analysis of SPRINT vs. natural history control arm.
作者信息
Adeyemi Ayo, Gross Andrea M, Baldwin Andrea, Dombi Eva, Widemann Brigitte C, Sint Kyaw Joe
机构信息
Health Economics and Outcomes Research, Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, USA.
Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
出版信息
Neurooncol Adv. 2025 May 17;7(1):vdaf101. doi: 10.1093/noajnl/vdaf101. eCollection 2025 Jan-Dec.
BACKGROUND
Selumetinib is approved in children aged ≥ 2 years (USA) with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN) based on data from SPRINT (NCT01362803). This analysis estimated PN progression risk with selumetinib in SPRINT versus age-matched patients from the National Cancer Institute NF1 Natural History (NH) study (NCT00924196), accounting for differences in baseline characteristics using propensity score (PS) methods.
METHODS
Differences in baseline characteristics between the cohorts were assessed. PSs based on age, sex, race, weight, height, and PN (location, volume, and progression status) were used in 1:1 PS matching without replacement, stabilized inverse probability of treatment weighting (sIPTW), and 1:2 PS matching with replacement as sensitivity analyses. The effect of selumetinib (maximum follow-up 5.6 years) on progression risk was evaluated using univariate and multivariable Cox models (adjusted for baseline characteristics) of progression-free survival.
RESULTS
Before PS matching, patient baseline characteristics ( = 50 SPRINT; = 75 NH) were generally balanced (standardized difference ≤ 0.2), except PN location (0.51) and PN status (0.60). Following 1:1 PS matching ( = 37), all characteristics were balanced except PN status (standardized difference 0.25). Balance was achieved with sIPTW and 1:2 PS matching ( = 46:43). Progression-free survival hazard ratios (95% confidence interval) were 0.11 (0.05-0.25), 0.11 (0.04-0.29), 0.12 (0.06-0.25), and 0.11 (0.06-0.24) (all < .001) for direct comparison, 1:1 PS matching, sIPTW, and 1:2 PS matching, respectively.
CONCLUSIONS
Reduction in risk of NF1-related PN progression with selumetinib was consistent with direct comparison and statistically significant, robust, and comparable across PS methods.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT01362803. Registered May 27, 2011, https://clinicaltrials.gov/study/NCT01362803.
背景
基于SPRINT（NCT01362803）的数据，塞鲁替尼已被批准用于年龄≥2岁（美国）的1型神经纤维瘤病（NF1）且患有症状性、无法手术的丛状神经纤维瘤（PN）的儿童患者。本分析通过倾向评分（PS）方法，估计了SPRINT研究中接受塞鲁替尼治疗的患者与美国国立癌症研究所NF1自然史（NH）研究（NCT00924196）中年龄匹配患者的PN进展风险，并考虑了基线特征的差异。
方法
评估了队列之间基线特征的差异。基于年龄、性别、种族、体重、身高和PN（位置、体积和进展状态）的PS用于无放回的1:1 PS匹配、稳定的逆概率治疗加权（sIPTW）以及作为敏感性分析的有放回的1:2 PS匹配。使用无进展生存期的单变量和多变量Cox模型（根据基线特征进行调整）评估塞鲁替尼（最长随访5.6年）对进展风险的影响。
结果
在PS匹配前，患者基线特征（SPRINT组n = 五十；NH组n = 七十五）总体平衡（标准化差异≤0.2），但PN位置（0.51）和PN状态（0.60）除外。在1:1 PS匹配后（n = 三十七），除PN状态（标准化差异0.25）外，所有特征均平衡。通过sIPTW和1:2 PS匹配（n = 四十六:四十三）实现了平衡。直接比较、1:1 PS匹配、sIPTW和1:2 PS匹配的无进展生存期风险比（95%置信区间）分别为0.11（0.05 - 0.25）、0.11（0.04 - 0.29）、0.12（0.06 - 0.25）和0.11（0.06 - 0.24）（均P <.001）。
结论
塞鲁替尼降低NF1相关PN进展风险的效果在直接比较中是一致的，并且在统计学上具有显著意义、稳健且在不同PS方法之间具有可比性。
试验注册
ClinicalTrials.gov，NCT01362803。于2011年5月27日注册，https://clinicaltrials.gov/study/NCT01362803 。
Zotero 插件