Department of Cancer Medicine, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France.
Eur J Cancer. 2019 Jul;115:97-106. doi: 10.1016/j.ejca.2019.04.020. Epub 2019 May 23.
Epidermal growth factor receptor (EGFR) and hepatocyte growth factor (HGF)/mesenchymal-epithelial transition (MET) pathways, which promote tumour growth and proliferation, are often deregulated in advanced gastroesophageal adenocarcinomas. We assessed whether adding panitumumab (an EGFR inhibitor) or rilotumumab (a HGF inhibitor) to first-line fluoropyrimidine-based and platinum-based chemotherapy (modified oxaliplatin, leucovorin and fluorouracil [mFOLFOX6]) benefits to patients with advanced gastroesophageal adenocarcinoma.
This phase II, open-label, randomised, three-arm study enrolled patients ≥18 years, with advanced gastroesophageal adenocarcinoma, Eastern Cooperative Oncology Group performance status 0-1 and no known HER2 overexpression. Patients were randomly assigned (1:1:1) mFOLFOX6 (oxaliplatin 85 mg/m, leucovorin 400 mg/m, 5-fluorouracil 400 mg/m bolus then 2400 mg/m over 46 h) alone or combined with panitumumab (6 mg/kg) or rilotumumab (10 mg/kg) every 2 weeks until limiting toxicity, patient's refusal or disease progression. The primary end-point was the 4-month progression-free survival (PFS) rate. Secondary end-points included overall survival (OS) and tolerance.
The study enrolled 162 patients in 29 French centres. The median follow-up was 23.6 months (interquartile range = 16.4-29.0). The 4-month PFS rate was 71% (95% confidence interval [CI] = 57-82) with chemotherapy alone, 57% (95% CI = 42-71) combined with panitumumab and 61% (95% CI = 47-74) combined with rilotumumab. Median OS was 13.1 months (95% CI = 8.7-16.9) with chemotherapy alone, 8.3 months (95% CI = 6.2-13.2) combined with panitumumab and 11.5 months (95% CI = 7.9-17.1) combined with rilotumumab. Adverse events grade ≥III occurred less frequently with chemotherapy alone (62%) than with panitumumab (83%) and rilotumumab (89%).
We found no benefit in adding panitumumab or rilotumumab to mFOLFOX6 first-line chemotherapy to treat advanced gastroesophageal adenocarcinoma patients.
European Clinical Trials Database, number 2009-012797-12.
表皮生长因子受体（EGFR）和肝细胞生长因子（HGF）/间质上皮转化（MET）通路促进肿瘤生长和增殖，在晚期胃食管腺癌中常发生失调。我们评估了在一线氟嘧啶类和铂类化疗（改良奥沙利铂、亚叶酸和氟尿嘧啶[mFOLFOX6]）的基础上加用panitumumab（一种 EGFR 抑制剂）或rilotumumab（一种 HGF 抑制剂）是否对晚期胃食管腺癌患者有益。
这是一项 II 期、开放性、随机、三臂研究，纳入了年龄≥18 岁、患有晚期胃食管腺癌、东部合作肿瘤组表现状态 0-1 级且无已知 HER2 过表达的患者。患者被随机分配（1:1:1）接受 mFOLFOX6（奥沙利铂 85mg/m2、亚叶酸 400mg/m2、5-氟尿嘧啶 400mg/m2 推注，然后 2400mg/m2 输注 46 小时）单独或联合 panitumumab（6mg/kg）或rilotumumab（10mg/kg）每 2 周一次，直至出现限制毒性、患者拒绝或疾病进展。主要终点是 4 个月无进展生存期（PFS）率。次要终点包括总生存期（OS）和耐受性。
该研究在法国的 29 个中心纳入了 162 名患者。中位随访时间为 23.6 个月（四分位距=16.4-29.0）。单独化疗的 4 个月 PFS 率为 71%（95%CI=57-82），联合 panitumumab 为 57%（95%CI=42-71），联合 rilotumumab 为 61%（95%CI=47-74）。单独化疗的中位 OS 为 13.1 个月（95%CI=8.7-16.9），联合 panitumumab 为 8.3 个月（95%CI=6.2-13.2），联合 rilotumumab 为 11.5 个月（95%CI=7.9-17.1）。III 级及以上不良事件发生率单独化疗（62%）低于 panitumumab（83%）和 rilotumumab（89%）。
我们发现，在 mFOLFOX6 一线化疗中加用 panitumumab 或 rilotumumab 并不能改善晚期胃食管腺癌患者的预后。
欧洲临床试验数据库，编号 2009-012797-12。
