作者：By Shreeya Nanda, Senior medwireNews Reporter
medwireNews: The combination of lenvatinib and etoposide plus ifosfamide has antitumour activity and manageable tolerability in patients with relapsed or refractory osteosarcoma, report trial investigators in柳叶刀肿瘤学。
Writing in a related commentary, Piotr Rutkowski, from the Maria Skłodowska-Curie National Research Institute of Oncology in Warsaw, Poland, says that based on these phase I/II results, “[w]e cannot definitively state that combining systemic chemotherapy with lenvatinib is a better option than standard treatment with etoposide plus ifosfamide or monotherapy with tyrosine kinase inhibitors.”
But he hopes that the ongoing randomised phase II trial of the combination will “shed light on the efficacy of antiangiogenic drugs as additives to systemic chemotherapy.”
The current study comprises multiple cohorts, including a dose-finding phase I cohort with 22 osteosarcoma patients aged 2–25 years and a phase II expansion cohort with 20 patients, all of whom had relapsed or refractory disease and had received no more than one prior VEGF- or VEGF receptor-targeted therapy, although there was no other limit regarding previous therapies.
在第一阶段，参与者以每天的每日剂量为11mg/m2（每天24mg），最多五个21天的依托泊苷100mg/m2 plus ifosfamide 3000mg/m2，以每天的每日剂量为11mg/m2（每天24mg）接受多激酶抑制剂lenvatinib。每个周期的1-3，随后持有单药lenvatinib，直到疾病进展或毒性为止。
Dose-limiting toxicities with the combination were observed in one patient receiving lenvatinib 11 mg/m2 per day and two patients receiving lenvatinib 14 mg/m2 per day, and the latter was determined as the recommended phase II dose, report Nathalie Gaspar, from Gustave Roussy Cancer Centre in Villejuif, France, and co-researchers.
然后，他们在任何一个队列中在建议的II期剂量下治疗的35例患者的数据汇总了数据，发现无进展生存期（PFS）在4个月中的二项式估计值为51％，而Kaplan-Meier-Meier估计值给出了率此时间点的80％。
PFS中值和总生存持续时间分别为8.7和16.3个月。
研究人员在报道了组合的毒性时说：“ [o] verall，与每种研究药物的安全性概况相一致的安全性，也没有观察到意外的不良事件。”
在汇总的lenvatinib每天14mg/m2组中，最常见的3-4级治疗急性不良事件是中性粒细胞减少症和血小板减少症，分别发生在77％和71％的参与者中，随后是贫血和减少的白血细胞和降低的白血细胞计数，分别为54％。
有两个5年级的事件 - 呼吸困难和恶性肿瘤进展的一个情况 - 但研究人员认为这些情况与研究治疗无关。
Discussing the findings, the study authors note that the PFS rate of 51% was higher “than that previously observed (32%) with lenvatinib 14 mg/m2 per day in the single-agent cohort of this study”, and is also “favourable compared with other studies in the same population” that show rates ranging from 42% with cyclophosphamide plus etoposide to 46% with sorafenib monotherapy, but they stress that cross-trial comparisons have limitations.
尽管如此，该小组认为，组合需要对该患者人群进行进一步的调查。
References
Gaspar N, Venkatramani R, Hecker-Nolting S,et al。Lenvatinib with etoposide plus ifosfamide in patients with refractory or relapsed osteosarcoma (ITCC-050):a multicentre, open-label, multicohort, phase 1/2 study.Lancet Oncol;提前在线出版物8月17日2021. doi：10.1016/s1470-2045（21）00387-9
Rutkowski P.抗血管生成剂与难治性骨肉瘤中的全身化疗相结合。Lancet Oncol;提前在线出版物8月17日2021. doi: 10.1016/S1470-2045(21)00422-8
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