Vergote Ignace B, Smith David C, Berger Raanan, Kurzrock Razelle, Vogelzang Nicholas J, Sella Avishay, Wheler Jennifer, Lee Yihua, Foster Paul G, Weitzman Ron, Buckanovich Ronald J
Division of Gynaecological Oncology, University Hospital Leuven, European Union, Leuven, Belgium.
Department of Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA.
Eur J Cancer. 2017 Sep;83:229-236. doi: 10.1016/j.ejca.2017.06.018. Epub 2017 Jul 26.
Cabozantinib (XL184), an orally bioavailable inhibitor of vascular endothelial growth factor receptor 2 and MET, was assessed in a cohort of ovarian carcinoma patients as part of a phase 2 randomised discontinuation trial (RDT) with cohorts from nine different tumour types.
Patients received 100-mg cabozantinib daily. Those with stable disease (SD) per Response Evaluation Criteria in Solid Tumors at week 12 were randomised to cabozantinib or placebo. Primary end-points were objective response rate (ORR) at week 12 and progression-free survival (PFS) after random assignment.
Seventy patients with ovarian carcinoma, 50% of whom were platinum refractory/resistant, were enrolled in this RDT. Median PFS from day 1 was 5.5 months for all patients. The ORR at week 12 was 21%; one patient achieved a complete response (CR), and 14 patients (20%) achieved a confirmed partial response (PR). The overall disease control rate (CR + PR + SD) at week 12 was 50%. Throughout the study, 70% of the patients with ≥1 postbaseline scan had tumour regression, and randomisation was discontinued early. For patients with SD randomised to cabozantinib, PFS was 5.9 months after randomisation. The most common grade 3/4 adverse events were diarrhoea (14%), palmar-plantar erythrodysesthesia syndrome (6%), asthenia (6%), hypertension (6%) and neutropenia (6%). Dose reductions were required in 37% of the patients during the first 12 weeks.
Cabozantinib demonstrates clinical activity, with acceptable toxicities, in patients with ovarian carcinoma based on ORR and regression of tumour target lesions.
This trial is registered at ClinicalTrial.gov (NCT00940225).
卡博替尼（XL184）是一种口服生物可利用的血管内皮生长因子受体2和MET抑制剂，作为一项2期随机停药试验（RDT）的一部分，在一组卵巢癌患者中进行了评估，该试验的队列来自9种不同肿瘤类型。
患者每日接受100 mg卡博替尼治疗。根据实体瘤疗效评价标准，在第12周病情稳定（SD）的患者被随机分为卡博替尼组或安慰剂组。主要终点为第12周的客观缓解率（ORR）和随机分组后的无进展生存期（PFS）。
70例卵巢癌患者入组该RDT，其中50%对铂类难治/耐药。所有患者从第1天起的中位PFS为5.5个月。第12周的ORR为21%；1例患者达到完全缓解（CR），14例患者（20%）达到确认的部分缓解（PR）。第12周的总体疾病控制率（CR + PR + SD）为50%。在整个研究过程中，70%的基线后至少有1次扫描的患者出现肿瘤消退，随机分组提前终止。对于随机分为卡博替尼组的SD患者，随机分组后的PFS为5.9个月。最常见的3/4级不良事件为腹泻（14%）、手足红斑感觉异常综合征（6%）、乏力（6%）、高血压（6%）和中性粒细胞减少（6%）。在最初12周内，37%的患者需要减量。
基于ORR和肿瘤靶病灶的消退，卡博替尼在卵巢癌患者中显示出临床活性，且毒性可接受。
本试验已在ClinicalTrial.gov注册（NCT00940225）。
