卡培他滨奥沙利铂（CAPOX）联合特瑞普利单抗短程放疗用于局部进展期直肠癌新辅助治疗的随机、前瞻性、多中心、双臂、Ⅱ期临床研究（TORCH）。
Short-course radiotherapy combined with CAPOX and Toripalimab for the total neoadjuvant therapy of locally advanced rectal cancer: a randomized, prospective, multicentre, double-arm, phase II trial (TORCH).
机构信息
Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
出版信息
BMC Cancer. 2022 Mar 15;22(1):274. doi: 10.1186/s12885-022-09348-z.
BACKGROUND
For patients with locally advanced (T3-4/N +) rectal cancer (LARC), the standard treatment is neoadjuvant chemoradiotherapy combined with total mesorectal resection, which greatly decreases local recurrence but does not improve overall survival. For patients who achieve a complete clinical response (cCR) after nCRT, a "Watch & Wait" (W&W) approach can be received to improve quality of life. Currently, total neoadjuvant therapy (TNT) has been demonstrated to increase the complete response rate and achieve early control of distant metastasis. Recent studies have shown promising synergistic effects of the combination of immunotherapy (PD-1/PD-L1 antibodies) and radiotherapy. Thus, for LARC patients, the combination of immunotherapy and TNT is likely to further improve the rate of complete response and prognosis. The disparities between induction therapy and consolidation therapy need to be investigated.
METHODS
TORCH is a randomized, prospective, multicentre, double-arm, phase II trial of short-course radiotherapy (SCRT) combined with chemotherapy and immunotherapy in LARC. 130 LARC patients will be treated with the TNT approach and assigned to the consolidation arm and induction arm. The consolidation arm will receive SCRT, followed by 6 cycles of capecitabine plus oxaliplatin (CAPOX) and Toripalimab. The induction arm will first receive 2 cycles of CAPOX and Toripalimab, then receive SCRT, followed by 4 cycles of CAPOX and Toripalimab. Both groups will receive curative surgery or the W&W strategy. The primary endpoint is the complete response rate (rate of pCR plus cCR). The secondary endpoints include the grade 3-4 acute adverse effects rate, 3-year disease-free survival (DFS) rate, 3-year local recurrence-free survival (LRFS) rate, 3-year OS rate, rate of surgical complications and quality of life (QoL) scores. The "pick the winner" method is used to investigate the better treatment regimen. The trial was opened on 13th April 2021, and the first patient was recruited on 6th May 2021.
DISCUSSION
TORCH will investigate whether SCRT combined with chemotherapy and Toripalimab can achieve better complete response rates, good tolerance and prognosis in LARC patients. This is the first clinical trial to compare the efficacy of induced immunotherapy and consolidative immunotherapy based on the TNT strategy.
TRIAL REGISTRATION
Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT04518280 , August 15, 2020.
背景
对于局部晚期（T3-4/N+）直肠癌（LARC）患者，标准治疗方法是新辅助放化疗联合直肠系膜全切除术，这大大降低了局部复发率，但并未改善总生存率。对于接受新辅助放化疗后达到完全临床缓解（cCR）的患者，可以采用“观察等待（W&W）”方法，以提高生活质量。目前，全新辅助治疗（TNT）已被证明可提高完全缓解率并早期控制远处转移。最近的研究表明，免疫疗法（PD-1/PD-L1 抗体）联合放疗具有良好的协同作用。因此，对于 LARC 患者，免疫治疗与 TNT 的联合应用可能进一步提高完全缓解率和预后。诱导治疗与巩固治疗之间的差异仍需要进一步研究。
方法
TORCH 是一项随机、前瞻性、多中心、双臂、二期临床试验，旨在研究短程放疗（SCRT）联合 LARC 化疗和免疫治疗的疗效。130 例 LARC 患者将接受 TNT 治疗，并分为巩固组和诱导组。巩固组接受 SCRT 治疗，随后接受 6 个周期的卡培他滨联合奥沙利铂（CAPOX）和特瑞普利单抗治疗。诱导组先接受 2 个周期的 CAPOX 和特瑞普利单抗治疗，然后接受 SCRT 治疗，随后再接受 4 个周期的 CAPOX 和特瑞普利单抗治疗。两组均接受根治性手术或 W&W 策略。主要终点是完全缓解率（pCR 率加 cCR 率）。次要终点包括 3-4 级急性不良反应发生率、3 年无病生存率（DFS）率、3 年局部无复发生存率（LRFS）率、3 年总生存率、手术并发症发生率和生活质量（QoL）评分。采用“胜者为王”法研究更好的治疗方案。该试验于 2021 年 4 月 13 日开始，首位患者于 2021 年 5 月 6 日入组。
讨论
TORCH 将研究 SCRT 联合化疗和特瑞普利单抗治疗 LARC 患者是否能获得更好的完全缓解率、良好的耐受性和预后。这是第一项基于 TNT 策略比较诱导性免疫治疗和巩固性免疫治疗疗效的临床试验。
试验注册
临床试验注册号和注册日期：ClinicalTrials.gov NCT04518280，2020 年 8 月 15 日。
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