Medical Oncology Department, Hospital Universitario Marqués de Valdecilla and Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain.
Medical Oncology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
Eur J Cancer. 2021 Mar;145:158-167. doi: 10.1016/j.ejca.2020.12.005. Epub 2021 Jan 20.
Perioperative chemotherapy improves overall survival (OS) and disease-free survival (DFS) compared with surgery alone in patients with resectable gastric adenocarcinoma (GA) or gastro-oesophageal junction adenocarcinoma (GEJA). The addition of trastuzumab to chemotherapy improves outcomes in patients with HER2-positive advanced gastric cancer (GC), and we aimed to explore its role in the perioperative setting.
This Spanish, multicentre, open-label phase II trial evaluated the efficacy and toxicity of perioperative capecitabine, oxaliplatin and trastuzumab (XELOX-T) in patients with HER2-positive resectable GA or GEJA. The primary end-point was 18-months DFS; and secondary end-points included pathological complete response (pCR) rate, R0 resection rate, OS and toxicity (NCT01130337).
Thirty-six patients were included. After three cycles of preoperative treatment, 14 patients (38% of the intention-to-treat population) had partial response and 18 (50%) had stable disease. Surgery was performed in 31 patients: 28 (90%) had R0 resection, three (9.6%) had a pCR and three (9.6%) died due to surgical complications. A total of 24 patients received post-operative XELOX-T, 22 of whom completed trastuzumab maintenance. Main grade III/IV toxicities included diarrhoea (33%), nausea and vomiting (8%). After a median follow-up of 24.1 months, 18-month DFS was 71% (95% confidence interval [CI], 53-83%); and an update after 102 months of follow-up showed a median OS of 79.9 months and a 60-month OS of 58% (95% CI, 40-73%).
These data suggest that perioperative XELOX-T in patients with HER2-positive GA and GEJA is feasible and active. Further investigation in randomised studies is warranted.
与单独手术相比，围手术期化疗可改善可切除胃腺癌（GA）或胃食管交界处腺癌（GEJA）患者的总生存期（OS）和无病生存期（DFS）。曲妥珠单抗联合化疗可改善 HER2 阳性晚期胃癌（GC）患者的预后，我们旨在探讨其在围手术期的作用。
这项西班牙多中心、开放标签的 II 期试验评估了可切除的 HER2 阳性 GA 或 GEJA 患者围手术期卡培他滨、奥沙利铂和曲妥珠单抗（XELOX-T）的疗效和毒性。主要终点为 18 个月 DFS；次要终点包括病理完全缓解（pCR）率、R0 切除率、OS 和毒性（NCT01130337）。
共纳入 36 例患者。在术前治疗的三个周期后，14 例患者（意向治疗人群的 38%）有部分缓解，18 例（50%）疾病稳定。31 例患者进行了手术：28 例（90%）行 R0 切除，3 例（9.6%）达 pCR，3 例（9.6%）因手术并发症死亡。共有 24 例患者接受了术后 XELOX-T 治疗，其中 22 例完成了曲妥珠单抗维持治疗。主要的 III/IV 级毒性包括腹泻（33%）、恶心和呕吐（8%）。中位随访 24.1 个月后，18 个月 DFS 为 71%（95%置信区间 [CI]，53-83%）；102 个月随访更新显示，中位 OS 为 79.9 个月，60 个月 OS 为 58%（95% CI，40-73%）。
这些数据表明，HER2 阳性 GA 和 GEJA 患者围手术期的 XELOX-T 是可行且有效的。需要进一步在随机研究中进行调查。
