SIREDO Oncology Center (Care, Innovation and Research for Children and AYA with Cancer), PSL Research University, Institut Curie, Paris.
Biometry Unit, Institut Curie, PSL Research University, Paris.
ESMO Open. 2024 May;9(5):103006. doi: 10.1016/j.esmoop.2024.103006. Epub 2024 Apr 23.
Patients with infantile fibrosarcoma (IFS) have shown strong and long-lasting responses to larotrectinib, a tropomyosin receptor kinase inhibitor (TRKi), in single-arm clinical trials. Conventional chemotherapy has also shown important efficacy. But, until now, no comparative data exist. This study aims to assess the therapeutic benefit of larotrectinib over the current standard of care (SOC) of chemotherapy in paediatric patients with locally advanced or metastatic IFS.
EPI VITRAKVI is a retrospective, observational, externally controlled study (NCT05236257). Data of patients aged ≤21 years with locally advanced or metastatic IFS treated with larotrectinib in the phase I/II SCOUT trial (NCT02637687) were compared with those of an external historical control group (data of Institut Curie and Cooperative Weichteilsarkom Studiengruppe) treated with a chemotherapy-based regimen. Between-group differences were assessed after balancing groups using inverse probability of treatment weighting (IPTW).
In total, 93 patients were compared, 51 in the larotrectinib arm and 42 in the external control arm. After therapy, 4 patients (7.8%) in the larotrectinib group had a medical treatment failure event [start of new systemic treatment (2 cases), mutilating surgery (2 cases)] versus 15 (35.7%) in the external control group [start of new systemic treatment (6 cases), mutilating surgery (5 cases), radiation therapy (2 cases), and death (2 cases)]. Larotrectinib was associated with an 80% reduced likelihood of encountering a medical treatment failure event, when compared to the external control group (weighted and stratified hazard ratio 0.20, 95% confidence interval 0.06-0.63, P = 0.0060). These results were confirmed by sensitivity analyses, including exact matching, and subgroup analyses for number of lines of treatment.
Treatment with larotrectinib reduced the need of subsequent therapies compared to SOC with chemotherapy in children with locally advanced or metastatic IFS, regardless of the line of treatment.
在单臂临床试验中，婴儿纤维肉瘤（IFS）患者对 Tropomyosin Receptor Kinase 抑制剂（TRKi）拉罗替尼表现出强烈且持久的反应。传统化疗也显示出重要的疗效。但是，到目前为止，尚无对照数据。本研究旨在评估拉罗替尼相对于目前婴儿局部晚期或转移性 IFS 患者的标准治疗（SOC）化疗的治疗获益。
EPI VITRAKVI 是一项回顾性、观察性、外部对照研究（NCT05236257）。将在 I 期/II 期 SCOUT 试验（NCT02637687）中接受拉罗替尼治疗的≤21 岁局部晚期或转移性 IFS 患者的数据与外部历史对照组（居里研究所和合作软组织肉瘤研究组的数据）进行比较，该对照组接受基于化疗的方案治疗。使用逆概率治疗加权（IPTW）平衡组后，评估组间差异。
共比较了 93 例患者，其中 51 例在拉罗替尼组，42 例在外部对照组。治疗后，拉罗替尼组有 4 例（7.8%）患者出现医疗治疗失败事件[开始新的全身治疗（2 例），破坏性手术（2 例）]，而外部对照组有 15 例（35.7%）患者出现医疗治疗失败事件[开始新的全身治疗（6 例），破坏性手术（5 例），放射治疗（2 例），死亡（2 例）]。与外部对照组相比，拉罗替尼治疗降低了 80%的医疗治疗失败事件发生几率（加权和分层风险比 0.20，95%置信区间 0.06-0.63，P=0.0060）。这些结果通过包括精确匹配和治疗线数亚组分析的敏感性分析得到了证实。
无论治疗线数如何，与 SOC 化疗相比，拉罗替尼治疗可降低局部晚期或转移性 IFS 儿童后续治疗的需求。
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