医脉通编译，转载请务必注明出处
2015年ASCO年会于5月29日—6月2日在美国芝加哥召开。5月31日上午的消化系统（非结直肠）肿瘤口头报告专场上，一项III期，随机，双盲，多中心，对照试验RILOMET-1研究，在晚期MET-阳性胃或胃食管交界处（G/GEJ）肿瘤患者中，将rilotumumab（R）联合表柔比星、顺铂和卡培他滨（ECX）作为一线方案治疗与安慰剂（P）进行比较。医脉通整理如下：
Rilotumumab（R）是一种肝细胞生长因子的完全人源化单克隆抗体。R+ECX vs P+ECX治疗MET-阳性G/GEJ肿瘤的II期临床试验显示R+ECX能够提高总生存期（OS）和无进展生存期（PFS）（参考文献：Lancet Oncol 2014；15:1007）。该项III期临床试验评估了R+ECX治疗MET-阳性G/GEJ肿瘤的疗效和安全性。
在研究中主要入组标准是，年龄≥18年；既往未经治疗，病理证实未不可切除的晚期G/GEJ腺癌；ECOG评分0-1分；肿瘤免疫组化MET阳性；HER2阴性。患者按1:1随机接受ECX（静脉表柔比星50mg/m2 D1，静脉顺铂60mg/m2 D1，口服卡培他滨625mg/m2 BID D1-21）联合R 15mg/kg或安慰剂（P）静脉Q3W治疗，对疾病侵及范围（局部晚期 vs 转移性）和ECOG评分（0 vs 1）进行分层。主要终点为OS。随机因素分层后，采用对数秩检验比较组间OS。本研究预计HR为0.69。关键次要终点是PFS，12个月存活率，客观缓解率（ORR），安全性和药代动力学（PK）。
在2012年11月至2014年11月，随机入组609例患者。该项研究因组间死亡病例失衡而提前终止（死亡病例R vs P：128 vs 107，截止数据：2014年11月27日）。R组OS并不优于P（组单侧检验，P值=0.99）。R组统计的OS，PFS和ORR更差。而且R组中所有的亚组均未见受益，包括MET表达≥1+的高表达肿瘤细胞人群。R组常见副反应（外周水肿，低蛋白血症，深静脉血栓和低钙血症）的发生率更高。
因此，RILOMET-1试验未达到研究主要终点；R组的OS更差，且差异具有统计意义。本研究的药代动力学和MET生物标志物分析仍在进行中。临床试验信息：NCT01697072。
会议专题》》》2015年ASCO年会专题报道
阅读原文摘要
Phase III, randomized, double-blind, multicenter, placebo (P)-controlled trial of rilotumumab (R) plus epirubicin, cisplatin and capecitabine (ECX) as first-line therapy in patients (pts) with advanced MET-positive (pos) gastric or gastroesophageal junction (G/GEJ) cancer: RILOMET-1 study.（Abstract 4000）
Authors：David Cunningham, Niall C. Tebbutt,et al.
Session Type：Oral Abstract Session
Background：R is a fully human monoclonal antibody to hepatocyte growth factor. A phase 2 study showed improved overall survival (OS) and progression-free survival (PFS) with R + ECX vs P + ECX in MET-pos G/GEJ cancer (Lancet Oncol 2014;15:1007). This phase 3 trial evaluated the efficacy and safety of R + ECX in MET-pos G/GEJ cancer.
Methods：Key eligibility criteria: ≥ 18 yr; previously untreated, pathologically confirmed unresectable advanced G/GEJ adenocarcinoma; ECOG score 0–1; tumor MET-pos by IHC; HER2-negative. Pts were randomized 1:1 to receive ECX (IV epirubicin 50 mg/m2 D1, IV cisplatin 60 mg/m2 D1, oral capecitabine 625 mg/m2BID D1−21) + R 15 mg/kg or P IV Q3W and stratified by disease extent (locally advanced vs metastatic) and ECOG score (0 vs 1). Primary endpoint: OS. A log-rank test stratified by randomization factors compared OS between arms. The study was powered to detect a HR of 0.69. Key secondary endpoints: PFS, 12-mo survival rate, objective response rate (ORR), safety and pharmacokinetics (PK).
Results：609 pts were randomized from Nov 2012 to Nov 2014. The study was stopped early based on an imbalance in deaths (R vs P: 128 vs 107 deaths, data cutoff: 27 Nov 2014). R was not superior to P for OS (one-sided test, p = 0.99). OS, PFS and ORR were statistically worse in the R arm. No subgroups seemed to benefit with R, including those with higher percentages of cells with ≥ 1+ MET expression. Most common AEs that were higher with R: peripheral edema, hypoalbuminemia, deep vein thrombosis and hypocalcemia.
Conclusions：RILOMET-1 did not meet its primary endpoint; OS was statistically significantly worse with R. PK and MET biomarker analyses are pending. Clinical trial information: NCT01697072
