2016-06-07 00:00:00来源：医脉通阅读：14次
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2016年6月3-7日，一年一度的美国临床肿瘤学会（American Society of Clinical Oncology，ASCO）年会在芝加哥举办。6月6日上午的消化系统（非结直肠）肿瘤口头报告专场上，一项摘要号为4007的随机双盲III期MAESTRO试验，在之前未接受治疗的转移性或局部晚期不可切除的胰腺导管腺癌（PDAC）患者中将evofosfamide（Evo）联合吉西他滨（Gem）进行研究，医脉通整理如下：
胰腺导管腺癌（PDAC）组织缺氧会带来疾病进展和较差预后。Evofosfamide（Evo）是一种Br-IPM缺氧-活化前药，在缺氧条件下优先激活。在一项晚期PDAC的随机II期试验中，Evo加入Gem会显著改善PFS（NCT01144455）。
MAESTRO是一项国际，随机，双盲，安慰剂-对照III期试验，该试验在局部晚期不可切除或转移性PDAC患者中将Evo/Gem与安慰剂（Pbo）/Gem进行比较（NCT01746979）。Evo 340mg/m2或者相匹配的Pbo和Gem 1000mg/m2在第1，8和15天IV给药，28天一个周期。关键合格标准包括ECOG PS 0/1。主要终点是总生存期（OS）。660例患者按照1:1随机分配，获得了508例事件（死亡）以保证90%P值来检出OS的0.75风险比（HR），双侧α为0.05。次要终点包括PFS和客观缓解率（ORR）。
2013年1月到2014年11月，693例患者被随机分配（346例Evo/Gem，347例Pbo/Gem）。基线特征均衡。中位OS分别为：Evo/Gem组8.7个月，Pbo/Gem组7.6个月；HR=0.84（95% CI：0.71-1.01，P=0.059）。中位PFS分别为：Evo/Gem组5.5个月，Pbo/Gem组3.7个月；HR=0.77（95% CI：0.65-0.92，P=0.004）。Evo/Gem组最佳ORR是20%，Pbo/Gem最佳ORR是16%；比值比（OR）=1.32（95% CI：0.88-1.97，P=0.17）。Evo/Gem组经证实的ORR是15%，Pbo/Gem组经证实的ORR是9%；OR=1.90（95% CI：1.16-3.12，P=0.009）。
最常见的非血液学AEs在各组相似：恶心（47%），食欲下降（35%）和
该项试验主要终点未满足OS的时间差异，不具有统计学显著性。Evo/Gem组显示抗肿瘤活性迹象，出现较长的PFS和较高的ORR。安全性与之前报道的类似。临床试验信息：NCT01746979。
会议专题》》》2016年ASCO年会专题报道
原文摘要：
MAESTRO: A randomized, double-blind phase III study of evofosfamide (Evo) in combination with gemcitabine (Gem) in previously untreated patients (pts) with metastatic or locally advanced unresectable pancreatic ductal adenocarcinoma (PDAC).（Abstract4007）
Authors：Eric Van Cutsem, Heinz-Josef Lenz,et al.
Session Type：Oral Abstract Session
Background: Hypoxia in PDAC is associated with disease progression and poor prognosis. Evo is a hypoxia-activated prodrug of Br-IPM that is preferentially activated under hypoxic conditions. The addition of Evo to Gem significantly improved PFS in a randomized phase II trial in advanced PDAC (NCT01144455).
Methods: MAESTRO was an international, randomized, double-blind, placebo-controlled phase III trial of Evo/Gem vs Placebo (Pbo)/Gem in pts with locally advanced unresectable or metastatic PDAC (NCT01746979). Evo 340 mg/m2 or matched Pbo and Gem 1,000 mg/m2 were administered IV on days 1, 8, and 15 of a 28-day cycle. Key eligibility criteria included ECOG PS 0/1. The primary endpoint was overall survival (OS). 660 patients were to be randomized 1:1 to obtain 508 events (deaths) to assure 90% power to detect a hazard ratio (HR) of 0.75 for OS with a two-sided α of 0.05. Secondary endpoints included PFS and objective response rate (ORR).
Results: From Jan 2013 to Nov 2014, 693 pts were randomized (346 Evo/Gem, 347 Pbo/Gem). Baseline characteristics were balanced. Median OS was 8.7 mo with Evo/Gem vs 7.6 mo with Pbo/Gem; HR = 0.84 (95% CI: 0.71–1.01, p = 0.059). Median PFS was 5.5 mo with Evo/Gem vs 3.7 mo with Pbo/Gem; HR = 0.77 (95% CI: 0.65–0.92, p = 0.004). Best ORR was 20% with Evo/Gem vs 16% with Pbo/Gem; odds ratio (OR) = 1.32 (95% CI: 0.88–1.97, p = 0.17). Confirmed ORR was 15% with Evo/Gem vs 9% with Pbo/Gem; OR = 1.90 (95% CI: 1.16 – 3.12, p = 0.009). Most common non-hematologic AEs of nausea (47%), decreased appetite (35%) and vomiting (33%) were similar across arms. Hematologic AEs of neutropenia, thrombocytopenia and anemia were more frequent with Evo/Gem. AEs leading to death were 9% with Evo/Gem vs 11% with Pbo/Gem. AEs leading to treatment discontinuation were 17.9% on Evo/Gem and 15.6% on Pbo/Gem.
Conclusions: The primary endpoint was not met as difference in OS time was not statistically significant. Evo/Gem showed signs of antitumor activity with longer PFS and higher ORR. The safety profile was similar to that previously reported. Clinical trial information: NCT01746979
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