Vogel Arndt, Römmler-Zehrer Josefine, Li Jack Shiansong, McGovern Desmond, Romano Alfredo, Stahl Michael
Department of Gastroenterology, Hepatology and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany.
Medizinische Hochschule Hannover, Ltd. Oberarzt der Klinik für Gastroenterologie, Hepatologie & Endokrinologie, Gebäude I11, Ebene H0, Raum 1380, Carl-Neubergstr. 1, 30625, Hannover, Germany.
BMC Cancer. 2016 Oct 21;16(1):817. doi: 10.1186/s12885-016-2798-8.
The phase 3 MPACT trial in patients with metastatic pancreatic cancer demonstrated superior efficacy of nab-paclitaxel (nab-P) + gemcitabine (Gem) vs Gem monotherapy for all endpoints examined including overall survival, the primary endpoint. In the MPACT trial, patients were treated until progressive disease (PD) or unacceptable toxicity. The current exploratory analysis investigated outcomes of patients from the MPACT trial who were treated until PD, in order to understand how to maximize treatment benefit from nab-P + Gem.
The trial design has been described in detail previously. Progressive disease was determined by the investigator on the basis of radiological imaging.
Among patients who were treated until PD, overall survival was significantly longer for those who received nab-P + Gem vs Gem (median, 9.8 vs 7.5 months; P < 0.001). Independently assessed progression-free survival and overall response rate were significantly greater among patients in the treatment-to-PD cohort who received nab-P + Gem compared with Gem (P < 0.001 for each). Although not compared statistically, patients who were treated until PD received greater treatment exposure and experienced more favourable efficacy than the intent-to-treat population of the MPACT trial. Among patients who were treated with nab-P + Gem until PD, > 50 % went on to receive a subsequent therapy. The safety profile for patients treated until PD was similar to what was reported in the overall MPACT trial.
The nab-P + Gem regimen is an active first-line treatment option; most patients were treated until PD, and this exposure was associated with improved efficacy outcomes. Prolonged first-line treatment exposure and ability to receive subsequent therapies likely contributed to the improved survival among these patients. Our data highlight the importance of managing adverse events and indicate that patients should be treated until PD when possible.
ClinicalTrials.gov NCT00844649 (MPACT trial); Registration date of this prospective phase III trial: February 13, 2009; current exploratory subanalysis was conducted retrospectively.
转移性胰腺癌患者的3期MPACT试验表明，与吉西他滨（Gem）单药治疗相比，白蛋白结合型紫杉醇（nab-P）+吉西他滨（Gem）在包括总生存期（主要终点）在内的所有研究终点上均显示出更高的疗效。在MPACT试验中，患者接受治疗直至疾病进展（PD）或出现不可接受的毒性。当前的探索性分析调查了MPACT试验中接受治疗直至PD的患者的结局，以了解如何从nab-P+Gem治疗中最大程度地获益。
试验设计先前已详细描述。疾病进展由研究者根据影像学检查确定。
在接受治疗直至PD的患者中，接受nab-P+Gem治疗的患者的总生存期明显长于接受Gem治疗的患者（中位数分别为9.8个月和7.5个月；P<0.001）。与接受Gem治疗的患者相比，接受nab-P+Gem治疗的治疗至PD队列患者的独立评估无进展生存期和总缓解率明显更高（每项P<0.001）。尽管未进行统计学比较，但接受治疗直至PD的患者比MPACT试验的意向性治疗人群接受了更多的治疗暴露，且疗效更佳。在接受nab-P+Gem治疗直至PD的患者中，超过50%的患者继续接受后续治疗。接受治疗直至PD的患者的安全性与MPACT试验总体报告的情况相似。
nab-P+Gem方案是一种有效的一线治疗选择；大多数患者接受治疗直至PD，这种治疗暴露与疗效改善相关。延长一线治疗暴露时间和接受后续治疗的能力可能有助于这些患者生存期的改善。我们的数据突出了管理不良事件的重要性，并表明患者应尽可能接受治疗直至PD。
ClinicalTrials.gov NCT00844649（MPACT试验）；这项前瞻性III期试验的注册日期：2009年2月13日；当前的探索性子分析是回顾性进行的。
