Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, 89681The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Medical Oncology, 89681The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231152350. doi: 10.1177/15330338231152350.
Chemotherapy combined with antivascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor monoclonal antibodies is the most promising approach to prolong survival and improve the quality of life of patients with unresectable metastatic colorectal cancer (mCRC). Anlotinib is an oral antiangiogenic tyrosine kinase inhibitor that targets VEGF receptors 1/2/3, fibroblast growth factor receptors 1-4, and platelet-derived growth factor receptors a/β. Since anlotinib combined with oxaliplatin and capecitabine (CAPEOX) as a first-line treatment was previously shown to be effective and safe for patients with wild-type (WT) mCRC, we designed this randomized, open-label, parallel-group, non-inferiority, phase III study to evaluate the efficacy and safety of anlotinib plus CAPEOX versus bevacizumab plus CAPEOX in patients with WT mCRC. The primary inclusion criteria are Eastern Cooperative Oncology Group performance status 0/1, confirmed WT colorectal adenocarcinoma, and unresectable metastases assessed by a multidisciplinary team. The main exclusion criteria are as follows: high microsatellite instability or deficient mismatch repair status, resectable or potentially resectable metastases, and previous systemic therapy for mCRC. A total of 698 patients will be randomized into the anlotinib and bevacizumab groups in a 1:1 ratio. Patients will receive 4 to 8 cycles of induction therapy (CAPEOX plus anlotinib or bevacizumab), followed by maintenance treatment (capecitabine plus anlotinib or bevacizumab) until disease progression or unacceptable toxicity. Progression-free survival (PFS) assessed by an independent review committee is the primary endpoint, whereas investigator-assessed PFS, overall survival, objective response rate, disease control rate, duration of response, resection rate of liver metastases, quality of life, and safety are the secondary endpoints. Enrollment commenced in May 2021. A prospective, randomized, phase III trial will provide a meaningful comparison of the efficacy and safety of anlotinib plus CAPEOX with standard treatment for patients with unresectable WT mCRC.
化疗联合抗血管内皮生长因子(VEGF)或表皮生长因子受体单克隆抗体是延长不可切除转移性结直肠癌(mCRC)患者生存时间和提高生活质量最有希望的方法。安罗替尼是一种口服抗血管生成酪氨酸激酶抑制剂，靶向 VEGF 受体 1/2/3、成纤维细胞生长因子受体 1-4 和血小板衍生生长因子受体 a/β。由于先前已经证明安罗替尼联合奥沙利铂和卡培他滨(CAPEOX)作为一线治疗对野生型(mCRC)患者有效且安全，因此我们设计了这项随机、开放标签、平行组、非劣效性、III 期研究，以评估安罗替尼联合 CAPEOX 与贝伐珠单抗联合 CAPEOX 在野生型(mCRC)患者中的疗效和安全性。主要纳入标准为东部肿瘤协作组(ECOG)体能状态 0/1，经多学科团队评估确认的野生型结直肠腺癌和不可切除的转移灶。主要排除标准为：高微卫星不稳定性或错配修复缺陷状态、可切除或潜在可切除的转移灶，以及先前用于 mCRC 的全身治疗。共 698 例患者将以 1:1 的比例随机分配至安罗替尼和贝伐珠单抗组。患者将接受 4 至 8 个周期的诱导治疗(CAPEOX 联合安罗替尼或贝伐珠单抗)，随后进行维持治疗(卡培他滨联合安罗替尼或贝伐珠单抗)，直至疾病进展或出现不可接受的毒性。由独立审查委员会评估的无进展生存期(PFS)是主要终点，而研究者评估的 PFS、总生存期、客观缓解率、疾病控制率、缓解持续时间、肝转移灶切除率、生活质量和安全性为次要终点。该研究于 2021 年 5 月开始入组。一项前瞻性、随机、III 期试验将为不可切除的野生型 mCRC 患者提供安罗替尼联合 CAPEOX 与标准治疗的疗效和安全性的有意义比较。
