文章：

局部食管或胃食管结合部腺癌术前及术后化疗联合阿特珠单抗治疗：一项I/II期单臂研究

Chemotherapy Plus Atezolizumab Pre- and Post-Resection in Localized Esophageal or Gastroesophageal Junction Adenocarcinomas: A Phase I/II Single-Arm Study

原文发布日期：31 March 2024

DOI: 10.3390/cancers16071378

类型: Article

开放获取: 是

英文摘要：

Efforts to improve the prognosis for patients with locally advanced esophageal or gastroesophageal junction (GEJ) adenocarcinoma have focused on neoadjuvant approaches to increase the pathological complete response (pathCR) rate, improve surgical resection, and prolong event-free and overall survival (OS). Building on the recent evidence that PD-1 inhibition plus chemotherapy improves the OS of patients with metastatic GEJ adenocarcinoma, we evaluated whether the application of this strategy in the neoadjuvant setting would improve the pathological response. This single-center phase I/II trial evaluated the safety, toxicity, and efficacy of neoadjuvant atezolizumab with oxaliplatin and 5-fluorouracil (modified FOLFOX) followed by esophagectomy followed by atezolizumab. The primary objective goal was to achieve 20% pathCR. From the twenty enrolled patients, eighteen underwent resection and two (10%, 95% CI: 1.24–31.7%) achieved pathCR. After a median follow-up duration of 40.7 months, 11 patients had disease recurrence and 10 had died. The median disease-free and OS were 28.8 (95% CI: 14.7, NA) and 38.6 months (95% CI: 30.5, NA), respectively. No treatment-related adverse events led to death. Although modified FOLFOX plus atezolizumab did not achieve the expected pathCR, an acceptable safety profile was observed. Our results support the continued development of a more refined strategy (neoadjuvant chemotherapy plus perioperative immunotherapy/targeted agents) with molecular/immune profiling in parallel.

摘要翻译： 

为改善局部晚期食管或胃食管结合部（GEJ）腺癌患者的预后，研究重点已转向新辅助治疗策略，旨在提高病理完全缓解（pathCR）率、优化手术切除效果，并延长无事件生存期和总生存期（OS）。基于近期证据表明PD-1抑制剂联合化疗可改善转移性GEJ腺癌患者的OS，本研究评估了将该策略应用于新辅助治疗阶段能否提升病理缓解率。这项单中心I/II期临床试验评估了新辅助阿特珠单抗联合奥沙利铂及5-氟尿嘧啶（改良FOLFOX方案）序贯食管切除术及术后阿特珠单抗治疗的安全性、毒性和疗效。主要目标为实现20%的pathCR率。在20例入组患者中，18例接受手术切除，其中2例（10%，95% CI：1.24–31.7%）达到pathCR。中位随访40.7个月后，11例患者出现疾病复发，10例死亡。中位无病生存期和总生存期分别为28.8个月（95% CI：14.7，不可用）和38.6个月（95% CI：30.5，不可用）。未发生治疗相关不良事件导致的死亡。尽管改良FOLFOX联合阿特珠单抗方案未达到预期pathCR目标，但其安全性特征可接受。本研究结果支持未来在分子/免疫分型指导下，继续开发更精细化的新辅助化疗联合围手术期免疫治疗/靶向治疗策略。

原文链接：

Chemotherapy Plus Atezolizumab Pre- and Post-Resection in Localized Esophageal or Gastroesophageal Junction Adenocarcinomas: A Phase I/II Single-Arm Study