Department of Medical Oncology, Kliniken Essen-Mitte, Essen, Germany.
Department of Internal Medicine II, University Clinic, Mainz, Germany.
Eur J Cancer. 2018 Apr;93:119-126. doi: 10.1016/j.ejca.2018.01.079. Epub 2018 Mar 20.
Perioperative chemotherapy significantly improves survival in patients with locally advanced oesophagogastric cancer (EGC). However, as approximately 60% of patients will die from their disease, new therapeutic agents such as molecular-targeted drugs are needed.
To evaluate the role of panitumumab with perioperative chemotherapy, previously untreated patients with locally advanced EGC received, in an open-label randomised phase II study (NEOPECX), standard epirubicin, cisplatin, capecitabine (ECX) chemotherapy with or without panitumumab. The primary end-point was the histological response rate after neoadjuvant therapy. The expression status and gene copy number of EGFR, HER2, and MET were determined by immunohistochemistry and fluorescence in situ hybridization (FISH). Plasma samples were collected before the first cycle of neoadjuvant chemotherapy.
Overall, 160 patients (80 versus 80) were eligible. The majority (82% versus 80%) showed lymph node involvement. Rate of R0-resection, percentage of patients with downstaging to ypT0-2 at pathohistological evaluation, and rate of major histological response was equal in both arms. Toxicity was increased by panitumumab with regard to thromboembolic events and skin toxicity. Patients with tumour EGFR, HER2 or MET expression had shorter progression-free and overall survival. FISH positivity for these markers was associated with shorter survival independent of therapy. High levels of soluble EGFR in particular predicted poor survival in the panitumumab arm.
The addition of panitumumab to ECX did not improve downstaging of locally advanced EGC. Low plasma levels of pathway-associated proteins such as sEGFR may identify a group of patients that benefit from EGFR-directed therapy. CLINICALTRIALS.GOV: NCT01234324.
围手术期化疗显著改善了局部晚期食管胃交界癌（EGC）患者的生存。然而，约 60%的患者将死于该疾病，因此需要新的治疗药物，如分子靶向药物。
为了评估帕尼单抗联合围手术期化疗在局部晚期 EGC 患者中的作用，一项开放标签随机 II 期研究（NEOPECX）入组了未经治疗的局部晚期 EGC 患者，接受标准表阿霉素、顺铂、卡培他滨（ECX）化疗联合或不联合帕尼单抗。主要终点是新辅助治疗后的组织学反应率。采用免疫组化和荧光原位杂交（FISH）检测 EGFR、HER2 和 MET 的表达状态和基因拷贝数。在新辅助化疗的第一个周期前采集血浆样本。
共有 160 例患者（80 例 vs 80 例）符合条件。大多数患者（82% vs 80%）存在淋巴结受累。R0 切除率、病理评估降期至 ypT0-2 的患者比例和主要组织学反应率在两组之间相当。帕尼单抗增加了血栓栓塞事件和皮肤毒性的发生率。肿瘤 EGFR、HER2 或 MET 表达的患者无进展生存期和总生存期更短。这些标志物的 FISH 阳性与独立于治疗的生存时间较短相关。特别是可溶性 EGFR 水平高预测了帕尼单抗组的不良预后。
在 ECX 基础上加用帕尼单抗并未改善局部晚期 EGC 的降期。与通路相关蛋白（如 sEGFR）的低血浆水平可能确定了一组从 EGFR 靶向治疗中获益的患者。临床试验。gov：NCT01234324。
