短程新辅助放化疗联合替雷利珠单抗治疗局部晚期食管鳞癌（SCALE-1）：一项单臂 Ib 期临床试验。
Short-course neoadjuvant radiotherapy combined with chemotherapy and toripalimab for locally advanced esophageal squamous cell carcinoma (SCALE-1): a single-arm phase Ib clinical trial.
机构信息
Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Pathology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
出版信息
J Immunother Cancer. 2024 Jan 9;12(1):e008229. doi: 10.1136/jitc-2023-008229.
BACKGROUND
The optimal dosages, timing, and treatment sequencing for standard-of-care neoadjuvant chemoradiotherapy necessitate re-evaluation when used in conjunction with immune checkpoint inhibitors for patients with resectable, locally advanced esophageal squamous cell carcinoma (RLaESCC). The SCALE-1 phase Ib study aimed to evaluate the safety and efficacy of short-course neoadjuvant radiotherapy combined with chemotherapy and toripalimab in this patient population.
METHODS
RLaESCC patients with clinical stages cT3-4aN0M0/cT1-4aN+M0 received neoadjuvant paclitaxel (135 mg/m), carboplatin (area under the curve=5), and toripalimab (240 mg) every 3 weeks for two cycles. Short-course neoadjuvant radiotherapy (30 Gy in 12 fractions; 5 days per week) was administered between neoadjuvant immune-chemotherapy (nICT) doses. Esophagectomies were scheduled 4-6 weeks after completing neoadjuvant treatment. The primary endpoint was safety, with secondary endpoints including pathological complete response (pCR) rate, postoperative complications, progression-free survival (PFS), and overall survival (OS). Exploratory biomarker analysis used gene expression profiles via the nCounter platform.
RESULTS
Of the 23 patients enrolled, all completed neoadjuvant radiotherapy, while 21 cases finished full nICT doses and cycles. Common grade 3/4 adverse events included neutropenia (57%), leukopenia (39%), and skin rash (30%). No grade 3 or higher esophagitis or pneumonitis occured. Twenty patients underwent surgery, and 11 achieved pCR (55%). Two patients (10%) experienced grade IIIb surgical complications. At the database lock, a 2-year PFS rate of 63.8% (95% CI 43.4% to 84.2%) and 2-year OS rate was 78% (95% CI 64.9% to 91.1%) were achieved. Tumor immune microenvironment analysis indicated that tumors with pCR exhibited significantly higher pretreatment T-cell-inflamed score and post-treatment reshaping of antitumor immunity.
CONCLUSIONS
Combining short-course neoadjuvant radiotherapy with chemotherapy and toripalimab demonstrated favorable safety and promising efficacy in RLaESCC patients.
TRIAL REGISTRATION NUMBER
ChiCTR2100045104.
背景
在可切除局部晚期食管鳞状细胞癌（RLaESCC）患者中，与免疫检查点抑制剂联合使用时，标准的新辅助放化疗的最佳剂量、时间和治疗顺序需要重新评估。SCALE-1 期 Ib 研究旨在评估短程新辅助放疗联合化疗和替雷利珠单抗在该患者人群中的安全性和有效性。
方法
临床分期为 cT3-4aN0M0/cT1-4aN+M0 的 RLaESCC 患者接受新辅助紫杉醇（135mg/m）、卡铂（曲线下面积=5）和替雷利珠单抗（240mg）每 3 周一次，共两个周期。短程新辅助放疗（30Gy，12 次；每周 5 天）在新辅助免疫化疗（nICT）剂量之间进行。新辅助治疗完成后 4-6 周安排行食管切除术。主要终点为安全性，次要终点包括病理完全缓解（pCR）率、术后并发症、无进展生存期（PFS）和总生存期（OS）。探索性生物标志物分析使用 nCounter 平台进行基因表达谱分析。
结果
23 例患者全部完成新辅助放疗，21 例完成全量 nICT 剂量和周期。常见的 3/4 级不良事件包括中性粒细胞减少（57%）、白细胞减少（39%）和皮疹（30%）。无 3 级或更高的食管炎或肺炎。20 例患者接受手术，11 例达到 pCR（55%）。2 例（10%）患者发生 IIIb 级手术并发症。在数据库锁定时，2 年 PFS 率为 63.8%（95%CI：43.4%至 84.2%），2 年 OS 率为 78%（95%CI：64.9%至 91.1%）。肿瘤免疫微环境分析表明，pCR 的肿瘤在预处理时具有更高的 T 细胞浸润评分，治疗后具有抗肿瘤免疫的重塑。
结论
短程新辅助放疗联合化疗和替雷利珠单抗在 RLaESCC 患者中显示出良好的安全性和有前景的疗效。
临床试验注册号
ChiCTR2100045104。
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