Prince of Wales Hospital, University of New South Wales, Sydney, NSW, Australia (DG); Royal Victoria Regional Health Centre, Barrie, ON, Canada (RHEM); Hôpital Beaujon, Clichy, France (PH); Klinikum Grosshadern, University of Munich, Munich, Germany (VH); Universitätsklinikum Würzburg, Würzburg, Germany (VK); Hospital Clinico San Carlos, Madrid, Spain (JS); Medizinische Universität Wien, Wien, Austria (WS); Ospedale Niguarda Ca' Granda, Milan, Italy (SS); Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain (JT); Hôpital Saint Antoine, Paris, France (LT); Azienda Ospedaliera Universitaria Integrata and University of Verona, Verona, Italy (GT); Hôpital Erasme, Brussels, Belgium (JLVL); Royal Hobart Hospital, Hobart, Australia (RY); Celgene Corporation, Summit, NJ (DNP); Celgene Corporation, Summit, NJ (BL); Celgene Corporation, Boudry, Switzerland (AR); Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale, AZ (DDVH).
J Natl Cancer Inst. 2015 Jan 31;107(2). doi: 10.1093/jnci/dju413. Print 2015 Feb.
Positive findings from the phase III MPACT trial led to the regulatory approval of nab-paclitaxel plus gemcitabine as a treatment option for patients with metastatic pancreatic cancer. This report is an update of overall survival (OS) based on longer follow-up.
Patients (n = 861) with metastatic pancreatic cancer and a Karnofsky performance status of 70 or greater were randomly assigned one to one to receive nab-paclitaxel + gemcitabine or gemcitabine alone. Efficacy data for this post hoc analysis were collected through May 9, 2013. Exploratory analyses of carbohydrate antigen 19-9 (CA19-9) and neutrophil-to-lymphocyte ratio (NLR) were conducted. The primary efficacy endpoint was OS, which was analyzed for all randomly assigned patients by the Kaplan-Meier method. All statistical tests were two-sided.
The median OS was statistically significantly longer for nab-paclitaxel plus gemcitabine vs gemcitabine alone (8.7 vs 6.6 months, hazard ratio [HR] = 0.72, 95% confidence interval [CI] = 0.62 to 0.83, P < .001). Long-term (>three-year) survivors were identified in the nab-paclitaxel plus gemcitabine arm only (4%). In pooled treatment arm analyses, higher CA19-9 level and NLR at baseline were statistically significantly associated with worse OS. There appeared to be a treatment effect for OS favoring nab-paclitaxel plus gemcitabine over gemcitabine alone in poor-prognosis subgroups defined by these factors (HR = 0.612, P < .001 for CA19-9 level ≥ median and HR = 0.81, P = .079 for NLR > 5).
These data confirm and extend the primary report of OS, supporting the superior efficacy of nab-paclitaxel plus gemcitabine over gemcitabine alone. Subgroup analyses support the relevance of CA 19-9 and NLR as prognostic markers in metastatic pancreatic cancer.
MPACT 三期临床试验的阳性结果促使监管部门批准纳布紫杉醇联合吉西他滨作为转移性胰腺癌患者的治疗选择。本报告基于更长时间的随访更新了总生存期（OS）数据。
患有转移性胰腺癌且 Karnofsky 表现状态评分为 70 或更高的患者按 1:1 随机分为接受纳布紫杉醇联合吉西他滨或吉西他滨单药治疗。本探索性分析的数据是通过 2013 年 5 月 9 日收集的。对碳水化合物抗原 19-9（CA19-9）和中性粒细胞与淋巴细胞比值（NLR）进行了探索性分析。主要疗效终点为 OS，通过 Kaplan-Meier 方法对所有随机分组患者进行分析。所有统计检验均为双侧检验。
纳布紫杉醇联合吉西他滨组的中位 OS 明显长于吉西他滨组（8.7 个月比 6.6 个月，风险比 [HR] = 0.72，95%置信区间 [CI] = 0.62 至 0.83，P<0.001）。仅在纳布紫杉醇联合吉西他滨组发现了长期（>三年）生存者（4%）。在联合治疗组分析中，基线时 CA19-9 水平和 NLR 较高与 OS 较差有统计学意义相关。对于这些因素定义的预后不良亚组，纳布紫杉醇联合吉西他滨治疗与吉西他滨单药治疗相比，OS 有获益的趋势（CA19-9 水平≥中位数时 HR = 0.612，P<0.001；NLR>5 时 HR = 0.81，P=0.079）。
这些数据证实并扩展了 OS 的主要报告，支持纳布紫杉醇联合吉西他滨优于吉西他滨单药治疗。亚组分析支持 CA19-9 和 NLR 作为转移性胰腺癌预后标志物的相关性。
