Department of Medical Oncology, Calvary Mater Newcastle, Waratah, Australia.
School of Medicine and Public Health, University of Newcastle, Callaghan, Australia.
Asia Pac J Clin Oncol. 2024 Jun;20(3):416-422. doi: 10.1111/ajco.14057. Epub 2024 Mar 21.
Many patients diagnosed with esophageal cancer have dysphagia from their primary tumor and de novo metastatic disease. The purpose of this study was to test the safety and efficacy of nivolumab given concurrently with hypofractionated chemoradiotherapy to patients with oligometastatic and obstructing esophageal tumors.
Patients were enrolled in a planned single-arm, phase 2 clinical trial. Eligible participants had previously untreated oligometastatic (≤5 metastases on fludeoxyglucose-18 positron emission tomography scan outside the primary tumor radiotherapy field) esophageal or gastroesophageal carcinoma, dysphagia, and Eastern Cooperative Oncology Group performance status 0-1. Treatment was with 2 weeks of concurrent hypofractionated radiotherapy (30 Gy/10#) to the primary tumor, weekly carboplatin AUC2, weekly paclitaxel 50 mg/m, and q2weekly nivolumab 240 mg, followed by nivolumab 480 mg continuing q4weekly until disease progression or 24 months total. A single metastasis was treated with stereotactic radiotherapy (SBRT) (24 Gy/3#) in week 7.
Five patients were recruited before trial closure to new participants for logistical reasons. Existing participants continued treatment per protocol as a pilot study at one center. All five patients completed chemoradioimmunotherapy and SBRT. All patients derived an improvement in their dysphagia. Two patients completed 24 months of nivolumab without disease progression. Grade 3 adverse events (AEs) occurred in 3 patients, however, there were no grade 4 AEs, AEs due to SBRT, or AEs of special interest as defined by the protocol.
Pilot results from five patients at one center found that treatment was well tolerated and effective for dysphagia relief. The efficacy of hypofractionated chemoradiotherapy with concurrent checkpoint inhibition should be tested in a multicentre study.
许多被诊断为食管癌的患者由于原发肿瘤和新转移疾病而出现吞咽困难。本研究的目的是测试在寡转移和阻塞性食管肿瘤患者中，纳武单抗联合低分割放化疗的安全性和疗效。
患者被纳入一项计划中的单臂、2 期临床试验。符合条件的参与者患有未经治疗的寡转移性（原发肿瘤放疗野外的氟脱氧葡萄糖-18 正电子发射断层扫描显示≤5 个转移灶）食管或胃食管交界癌、吞咽困难和东部合作肿瘤组表现状态 0-1。治疗方案为 2 周同步低分割放疗（30Gy/10#），原发肿瘤、每周卡铂 AUC2、每周紫杉醇 50mg/m2，以及 q2 周纳武单抗 240mg，然后继续每 4 周纳武单抗 480mg，直到疾病进展或总共 24 个月。在第 7 周，单个转移灶采用立体定向放疗（SBRT）（24Gy/3#）治疗。
由于后勤原因，在试验关闭前，有 5 名患者被招募到新的参与者中。根据协议，现有参与者继续进行治疗，作为一个中心的试点研究。所有 5 名患者均完成了放化疗免疫治疗和 SBRT。所有患者的吞咽困难均有所改善。2 名患者在无疾病进展的情况下完成了 24 个月的纳武单抗治疗。3 名患者发生了 3 级不良事件（AE），然而，没有 4 级 AE、SBRT 引起的 AE 或协议定义的特殊关注的 AE。
来自一个中心的 5 名患者的试点结果发现，治疗耐受性良好，对缓解吞咽困难有效。应在多中心研究中测试低分割放化疗联合检查点抑制的疗效。
