Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan; Hubei Key Laboratory of Precision Radiation Oncology, Wuhan; Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.
Ann Oncol. 2024 Oct;35(10):882-891. doi: 10.1016/j.annonc.2024.06.015. Epub 2024 Jul 2.
BACKGROUND: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a programmed cell death protein 1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC. PATIENTS AND METHODS: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1 : 1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by two cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either six cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or six cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS). RESULTS: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in the experimental arm and 118 patients in the control arm, with surgery carried out in 92% and 83.9%, respectively. At data cut-off (11 July 2023), the pCR rates were 39.8% [95% confidence interval (CI) 30.7% to 49.5%] in the experimental arm compared to 15.3% (95% CI 9.3% to 23.0%) in the control arm (difference, 24.6%; odds ratio, 3.7; 95% CI 2.0-6.9; P < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, and grade ≥3 treatment-related adverse events were 29.2% and 27.2%. Three-year EFS rate and OS continue to mature. CONCLUSIONS: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients.
背景：在一项 II 期临床试验中，新辅助短程放疗（SCRT）后加用 CAPOX 和卡瑞利珠单抗（一种程序性死亡蛋白 1 单克隆抗体）显示出对局部晚期直肠癌（LARC）的潜在临床活性。本研究旨在进一步证实 SCRT 后加用 CAPOX 和卡瑞利珠单抗与长程放化疗（LCRT）后加用 CAPOX 作为 LARC 新辅助治疗相比的疗效和安全性。
患者和方法：在这项随机、III 期试验中，T3-4/N+直肠腺癌患者按 1:1 随机分配接受 SCRT 或长程放化疗（LCRT），随后分别接受 2 周期卡瑞利珠单抗加 CAPOX 或 CAPOX 单药治疗。手术后，每个臂分别接受 6 周期卡瑞利珠单抗加 CAPOX，随后加用至多 17 剂卡瑞利珠单抗，或 6 周期 CAPOX。主要终点是通过盲法独立评估委员会评估的病理完全缓解率（ypT0N0）。分层检验的关键次要终点是 3 年无事件生存率（EFS）和总生存率（OS）。
结果：2021 年 7 月至 2023 年 3 月，意向治疗人群中实验组有 113 例患者，对照组有 118 例患者，手术分别完成 92%和 83.9%。在数据截止日期（2023 年 7 月 11 日）时，实验组的病理完全缓解率为 39.8%（95%置信区间 [CI] 30.7%至 49.5%），对照组为 15.3%（95% CI 9.3%至 23.0%）（差异，24.6%；比值比，3.7；95% CI 2.0-6.9；P<0.001）。在每个臂中，手术并发症发生率分别为 40.0%和 40.8%，≥3 级治疗相关不良事件发生率分别为 29.2%和 27.2%。3 年 EFS 率和 OS 继续成熟。
结论：在 LARC 患者中，SCRT 后加用卡瑞利珠单抗加 CAPOX 与 LCRT 后加用 CAPOX 相比，pCR 率显著提高，安全性可耐受。SCRT 后加用卡瑞利珠单抗和化疗可作为这些患者的新辅助治疗方法。
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