比较纳米聚合物胶束紫杉醇和溶剂型紫杉醇作为晚期非小细胞肺癌一线治疗药物的疗效：一项开放标签、随机、多中心、III 期临床试验。

Comparing nanoparticle polymeric micellar paclitaxel and solvent-based paclitaxel as first-line treatment of advanced non-small-cell lung cancer: an open-label, randomized, multicenter, phase III trial.

机构信息

Department of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.

Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

出版信息

Ann Oncol. 2021 Jan;32(1):85-96. doi: 10.1016/j.annonc.2020.10.479. Epub 2020 Oct 29.

DOI:10.1016/j.annonc.2020.10.479

PMID:33130217

Abstract

BACKGROUND

Polymeric micellar paclitaxel (pm-Pac) is a novel Cremophor EL-free, nanoparticle micellar formulation of paclitaxel. We aimed to compare the efficacy and safety between pm-Pac plus cisplatin and solvent-based paclitaxel (sb-Pac) plus cisplatin in advanced non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS

A total of 448 stage IIIB to IV NSCLC patients were randomly assigned (2:1) to receive six 3-week cycles of either pm-Pac (230 mg/m) plus cisplatin (70 mg/m; n = 300), followed by dose escalation of pm-Pac to 300 mg/m from the second 3-week cycle if prespecified toxic effects were not observed after the first cycle, or sb-Pac (175 mg/m) plus cisplatin (70 mg/m; n = 148). The primary end point was objective response rate (ORR) assessed by independent review committees (IRCs). The secondary end points included IRC-assessed progression-free survival (PFS), overall survival (OS), and safety.

RESULTS

Patients in the pm-Pac-plus-cisplatin group showed significant improvements in IRC-assessed ORR compared with those in the sb-Pac-plus-cisplatin group (50% versus 26%; rate ratio 1.91; P < 0.0001). Additionally, subgroup analysis showed that a higher ORR was consistently observed in both squamous and nonsquamous histological types. IRC-assessed median PFS was significantly higher in the pm-Pac-plus-cisplatin group than in the sb-Pac-plus-cisplatin group (6.4-month versus 5.3-month; hazard ratio 0.63; P = 0.0001). Median OS was not significantly different between the two groups. The incidence of treatment-related serious adverse events (9% versus 18%; P = 0.0090) was significantly lower in the pm-Pac-plus-cisplatin group than in the sb-Pac-plus-cisplatin group.

CONCLUSION

Pm-Pac plus cisplatin yielded superior ORR and PFS along with a favorable safety profile and should become an option for patients with advanced NSCLC.

CLINICAL TRIAL IDENTIFIER

ClinicalTrials.gov NCT02667743; https://clinicaltrials.gov/ct2/show/NCT02667743.

摘要

背景

聚乙二醇化紫杉醇胶束（pm-Pac）是一种新型无聚氧乙烯蓖麻油的紫杉醇纳米胶束制剂。我们旨在比较聚乙二醇化紫杉醇胶束联合顺铂与溶剂型紫杉醇（sb-Pac）联合顺铂治疗晚期非小细胞肺癌（NSCLC）的疗效和安全性。

患者和方法

共 448 例 IIIB 至 IV 期 NSCLC 患者被随机分配（2:1）接受 6 个 3 周周期的治疗，pm-Pac（230mg/m）联合顺铂（70mg/m；n=300），或 sb-Pac（175mg/m）联合顺铂（70mg/m；n=148）。主要终点为独立审查委员会（IRC）评估的客观缓解率（ORR）。次要终点包括 IRC 评估的无进展生存期（PFS）、总生存期（OS）和安全性。

结果

pm-Pac 联合顺铂组的 IRC 评估 ORR 明显高于 sb-Pac 联合顺铂组（50%比 26%；率比 1.91；P<0.0001）。此外，亚组分析显示，在鳞癌和非鳞癌组织学类型中均观察到更高的 ORR。pm-Pac 联合顺铂组 IRC 评估的中位 PFS 明显长于 sb-Pac 联合顺铂组（6.4 个月比 5.3 个月；风险比 0.63；P=0.0001）。两组中位 OS 无显著差异。pm-Pac 联合顺铂组治疗相关严重不良事件（9%比 18%；P=0.0090）的发生率明显低于 sb-Pac 联合顺铂组。