A multi-national, randomised, open-label, parallel, phase III non-inferiority study comparing NK105 and paclitaxel in metastatic or recurrent breast cancer patients
A multi-national, randomised, open-label, parallel, phase III non-inferiority study comparing NK105 and paclitaxel in metastatic or recurrent breast cancer patients
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DOI：
10.1038/s41416-019-0391-z
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发表时间：
2019-03-05
影响因子：
8.8
通讯作者：
Nambu, Yoshihiro
中科院分区：
文献类型：
--
作者：
Fujiwara, Yasuhiro;Mukai, Hirofumi;Nambu, Yoshihiro
背景：NK105是一种新型的纳米颗粒给药制剂，它将紫杉醇（PTX）包裹在聚合物胶束中。我们进行了一项开放标签III期非劣效性试验，比较NK105和PTX治疗转移性或复发性乳腺癌的疗效和安全性。方法：患者以1:1的比例随机分配，在28天周期的第1、8和15天接受NK105 （65 mg/m(2)）或PTX （80 mg/m(2)）。主要终点为无进展生存期（PFS），非劣效性裕度为1.215。结果：共纳入436例患者，每组211例纳入疗效分析。NK105和PTX的中位PFS分别为8.4和8.5个月（校正风险比：1.255；95%可信区间：0.989-1.592）。中位总生存期和总缓解率分别为31.2个月和36.2个月，31.6%和39.0%。两组表现出相似的安全性。NK105和PTX的周围感觉神经病变（PSN）发生率分别为1.4%和7.5%（>= 3级）。患者报告的PSN结果对NK105显著有利（P < 0.0001）。结论：主要终点未达到，但NK105具有比PTX更好的PSN毒性。
BACKGROUND: NK105 is a novel nanoparticle drug delivery formulation that encapsulates paclitaxel (PTX) in polymeric micelles. We conducted an open-label phase III non-inferiority trial to compare the efficacy and safety of NK105 and PTX in metastatic or recurrent breast cancer.METHODS: Patients were randomly assigned in a 1:1 ratio to receive either NK105 (65 mg/m(2)) or PTX (80 mg/m(2)) on days 1, 8 and 15 of a 28-day cycle. The primary endpoint was progression-free survival (PFS), with a non-inferiority margin of 1.215.RESULTS: A total of 436 patients were randomised and 211 patients in each group were included in the efficacy analysis. The median PFS was 8.4 and 8.5 months for NK105 and PTX, respectively (adjusted hazard ratio: 1.255; 95% confidence interval: 0.989-1.592). The median overall survival and overall response rates were 31.2 vs. 36.2 months and 31.6% vs. 39.0%, respectively. The two groups exhibited similar safety profiles. The incidence of peripheral sensory neuropathy (PSN) was 1.4% vs. 7.5% (>= Grade 3) for NK105 and PTX, respectively. The patient-reported outcomes of PSN were significantly favourable for NK105 (P < 0.0001).CONCLUSIONS: The primary endpoint was not met, but NK105 had a better PSN toxicity profile than PTX.