一项多中心、随机、开放标签、平行对照、III 期非劣效性研究，旨在比较 NK105 与紫杉醇在转移性或复发性乳腺癌患者中的疗效。
A multi-national, randomised, open-label, parallel, phase III non-inferiority study comparing NK105 and paclitaxel in metastatic or recurrent breast cancer patients.
机构信息
Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan.
Division of Breast and Medical Oncology, National Cancer Center Hospital East, Chiba, Japan.
出版信息
Br J Cancer. 2019 Mar;120(5):475-480. doi: 10.1038/s41416-019-0391-z. Epub 2019 Feb 12.
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) or PTX (80 mg/m) 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.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov: NCT01644890.
背景
NK105 是一种新型的纳米药物递送制剂，将紫杉醇（PTX）封装在聚合物胶束中。我们进行了一项开放标签的 III 期非劣效性试验，以比较 NK105 与 PTX 在转移性或复发性乳腺癌中的疗效和安全性。
方法
患者以 1:1 的比例随机分配，接受 NK105（65mg/m）或 PTX（80mg/m）治疗，每 28 天周期的第 1、8 和 15 天给药。主要终点是无进展生存期（PFS），非劣效性边界为 1.215。
结果
共随机分配了 436 名患者，每组 211 名患者纳入疗效分析。NK105 和 PTX 的中位 PFS 分别为 8.4 个月和 8.5 个月（调整后的危险比：1.255；95%置信区间：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%。两组的安全性谱相似。周围感觉神经病变（PSN）的发生率分别为 NK105 的 1.4%和 PTX 的 7.5%（≥3 级）。NK105 的 PSN 患者报告结局明显优于 PTX（P<0.0001）。
结论
主要终点未达到，但 NK105 的 PSN 毒性谱优于 PTX。
临床试验注册
ClinicalTrials.gov：NCT01644890。
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