一项评估纳武利尤单抗作为术前多西他赛、顺铂加氟尿嘧啶治疗（PENTAGON 试验）后食管癌患者术后辅助治疗的疗效和安全性的 II 期研究方案。
Protocol for a phase II study to evaluate the efficacy and safety of nivolumab as a postoperative adjuvant therapy for patients with esophageal cancer treated with preoperative docetaxel, cisplatin plus 5-fluorouracil treatment (PENTAGON trial).
机构信息
Division of Gastrointestinal Surgery, Department of Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan.
Division of Medical Oncology and Hematology, Department of Medicine, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan.
出版信息
PLoS One. 2024 Apr 18;19(4):e0299742. doi: 10.1371/journal.pone.0299742. eCollection 2024.
BACKGROUND
In Japan, preoperative adjuvant chemotherapy followed by surgical resection is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma. However, the risk of recurrence after surgical resection remains high. Although a randomized controlled trial evaluating the efficacy of nivolumab, a fully human monoclonal anti-programmed death 1 antibody, as postoperative adjuvant therapy after neoadjuvant chemoradiotherapy and surgery established its superior efficacy as adjuvant therapy, the efficacy for patients who received preoperative adjuvant chemotherapy has not been demonstrated. This study aims to elucidate the efficacy and safety of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection.
METHODS
This study is a multi-institutional, single-arm, Phase II trial. We plan to recruit 130 esophageal squamous cell carcinoma patients, who have undergone preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. If the patient did not have a pathological complete response, nivolumab is started as a postoperative adjuvant therapy within 4-16 weeks after surgery. The nivolumab dose is 480 mg/day every four weeks. Nivolumab is administered for up to 12 months. The primary endpoint is disease-free survival; the secondary endpoints are overall survival, distant metastasis-free survival, and incidence of adverse events.
DISCUSSION
To our knowledge this study is the first trial establishing the efficacy of nivolumab as postoperative adjuvant therapy for patients with esophageal squamous cell carcinoma after preoperative adjuvant chemotherapy with docetaxel and cisplatin plus 5-fluorouracil followed by surgical resection. In Japan, preoperative adjuvant chemotherapy followed by surgery is a well-established standard treatment for resectable, locally advanced esophageal squamous cell carcinoma. Therefore, developing an effective postoperative adjuvant therapy has been essential for improving oncological outcomes.
背景
在日本，对于局部晚期食管鳞癌患者，术前辅助化疗后行手术切除是标准治疗方法。然而，手术后复发的风险仍然很高。尽管一项评价纳武利尤单抗（一种完全人源化抗程序性死亡 1 单克隆抗体）作为新辅助放化疗及手术治疗后辅助治疗的疗效的随机对照临床试验证实了其作为辅助治疗的优越性，但术前辅助化疗患者的疗效尚未得到证实。本研究旨在阐明纳武利尤单抗作为术前接受多西他赛和顺铂联合氟尿嘧啶辅助化疗加手术切除的食管鳞癌患者术后辅助治疗的疗效和安全性。
方法
这是一项多机构、单臂、Ⅱ期临床试验。我们计划招募 130 例接受多西他赛和顺铂联合氟尿嘧啶术前辅助化疗加手术切除的食管鳞癌患者。如果患者没有病理完全缓解，在手术后 4-16 周内开始纳武利尤单抗作为术后辅助治疗。纳武利尤单抗剂量为 480 mg/天，每四周一次。纳武利尤单抗治疗持续 12 个月。主要终点是无病生存；次要终点是总生存、无远处转移生存和不良反应发生率。
讨论
据我们所知，这是第一项在术前接受多西他赛和顺铂联合氟尿嘧啶辅助化疗加手术切除的患者中确立纳武利尤单抗作为术后辅助治疗疗效的临床试验。在日本，术前辅助化疗加手术是可切除局部晚期食管鳞癌的既定标准治疗方法。因此，开发有效的术后辅助治疗方法对于改善肿瘤学结果至关重要。
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