评价针对微卫星稳定/高错配修复转移性结直肠腺癌患者中对酪氨酸激酶抑制剂有反应者的酪氨酸激酶抑制剂联合抗程序性细胞死亡蛋白 1 抗体：一项开放标签、单臂试验的方案。
Evaluation of tyrosine kinase inhibitors combined with antiprogrammed cell death protein 1 antibody in tyrosine kinase inhibitor-responsive patients with microsatellite stable/proficient mismatch repair metastatic colorectal adenocarcinoma: protocol for open-label, single-arm trial.
机构信息
Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of China Medical University, Shenyang, Liaoning, China.
Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital & Institute, Cancer Hospital of China Medical University, Shenyang, Liaoning, China
出版信息
BMJ Open. 2022 Apr 4;12(4):e049992. doi: 10.1136/bmjopen-2021-049992.
INTRODUCTION
The prognosis of patients with advanced metastatic colorectal adenocarcinoma (mCRC) after multiple-line therapy remains poor due to the high tumour load, high level of malignancy and strong drug resistance. The application of programmed cell death protein 1 (PD-1) blockade alone for patients with microsatellite stable/proficient mismatch repair (MSS/pMMR) mCRC is ineffective. PD-1 blockade combined with antiangiogenic therapy has synergistic effects and has initially shown therapeutic effects. The aim of this trial is to explore the efficiency and safety of tyrosine kinase inhibitors (TKIs) combined with PD-1 blockade therapy in patients with mCRC with MSS/pMMR.
METHODS AND ANALYSIS
The screening phase of the trial will involve administering one cycle of TKIs (fruquintinib or regorafenib). Patients will be divided into three arms-arm A (obvious response to TKIs), arm B (general response to TKIs) and arm C (poor response to TKIs)-according to their response to TKIs, as determined by significant changes in imaging findings. Patients in arm A will then receive TKIs in combination with anti-PD-1 antibody, patients in arm C will withdraw from the study, and those in arm B will continue to take TKIs for another one further cycle. Next, patients with obvious response to TKIs will be reallocated to arm A, those with general response to TKIs will stay in arm B and will continue to take TKIs, and patients with poor response to TKIs will withdraw from the study. Administration of arm A or arm B will last until disease progression or intolerable toxicity. Anti-PD-1 antibody can be administered for up to 2 years. This trial will provide necessary data to improve the prognosis of patients with MSS/pMMR mCRC.
TRIAL REGISTRATION NUMBER
NCT04483219; Pre-results.
简介
由于肿瘤负荷高、恶性程度高、耐药性强，接受多线治疗后的晚期转移性结直肠腺癌（mCRC）患者预后仍然较差。单独应用程序性死亡蛋白 1（PD-1）阻断剂治疗微卫星稳定/高错配修复（MSS/pMMR）mCRC 患者无效。PD-1 阻断联合抗血管生成治疗具有协同作用，初步显示出治疗效果。本试验旨在探讨 PD-1 阻断联合酪氨酸激酶抑制剂（TKI）治疗 MSS/pMMR mCRC 患者的疗效和安全性。
方法与分析
试验的筛选阶段将给予一个周期的 TKI（呋喹替尼或瑞戈非尼）。根据影像学检查结果的显著变化，患者将根据对 TKI 的反应分为三组：A 组（TKI 明显有效）、B 组（TKI 一般有效）和 C 组（TKI 效果不佳）。A 组患者随后接受 TKI 联合抗 PD-1 抗体治疗，C 组患者将退出研究，B 组患者将继续接受另一个周期的 TKI 治疗。然后，对 TKI 有明显反应的患者将重新分配到 A 组，对 TKI 有一般反应的患者将留在 B 组，并继续接受 TKI 治疗，对 TKI 反应不佳的患者将退出研究。A 组或 B 组的治疗将持续到疾病进展或无法耐受毒性。抗 PD-1 抗体的使用最长可达 2 年。本试验将提供必要的数据，以改善 MSS/pMMR mCRC 患者的预后。
试验注册号
NCT04483219；预结果。
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