Lessons learned: Patients with metastatic colorectal cancer with good performance status or no liver metastasis could benefit from apatinib.Circulating tumor DNA abundance may be a predictor in serial monitoring of tumor load.
Background: Apatinib, an oral vascular endothelial growth factor (VEGF) receptor-2 inhibitor, has been approved as third-line treatment for metastatic gastric cancer in China. The aim of this study was to evaluate the efficacy and safety of apatinib, in the treatment of patients with refractory metastatic colorectal cancer after failure of two or more lines of chemotherapy.
Methods: In this open-label, single-arm, phase II study, patients with histological documentation of adenocarcinoma of the colon or rectum were eligible if they had received at least two prior regimens of standard therapies including fluoropyrimidine, oxaliplatin, and irinotecan. These patients were treated with apatinib in a daily dose of 500 mg, p.o., in the third-line or higher setting. Capture sequencing was dynamically performed to identify somatic variants in circulating tumor DNA (ctDNA) with a panel of 1,021 cancer-related genes. The primary endpoint was progression-free survival (PFS) and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Interim analysis was applied as predefined.
Results: From June 1, 2016 to December 31, 2017, 26 patients were enrolled. The median PFS of the whole group was 3.9 months (95% confidence interval [CI]: 2.1-5.9). The median overall survival (OS) was 7.9 months (95% CI: 4.6-10.1+). Patients with performance status (PS) 0-1 had longer PFS than those with PS 2 (4.17 months vs. 1.93 months, p = .0014). Patients without liver metastasis also had longer PFS than those who had live metastasis (5.87 months vs. 3.33 months, p = .0274). The common side effects of apatinib were hypertension, hand-foot syndrome, proteinuria, and diarrhea. The incidence of grade 3-4 hypertension, hand-foot syndrome, proteinuria, and diarrhea was 76.92%, 11.54%, 73.08%, and 23.08%, respectively. All of the patients received dose reduction because of adverse effect. Results of capture sequencing showed APC, TP53, and KRAS were most frequently mutant genes. ctDNA abundance increased before the radiographic assessment in ten patients.
Conclusion: Apatinib monotherapy showed promising efficiency for patients with refractory colorectal cancer, especially in patients with PS 0-1 or no liver metastasis. ctDNA abundance may be a predictor in serial monitoring of tumor load.
经验获取
体力状态良好或无肝脏转移的转移性结直肠癌患者可受益于阿帕替尼。
循环肿瘤 DNA 丰度可能是肿瘤负荷连续监测的预测因子。
摘要
背景。阿帕替尼是一种口服血管内皮生长因子 (VEGF) 受体‐ 2 抑制剂，在中国已被批准作为转移性胃癌的三线治疗药物。本研究的目的是评估阿帕替尼治疗二线或二线以上化疗失败的难治性转移性结直肠癌患者的疗效和安全性。
方法。在这项开放标签单组 II 期研究中，如果组织学记录患有结肠或直肠腺癌的患者之前至少接受过两种标准疗法方案(包括氟尿嘧啶、奥沙利铂和伊立替康)，则符合研究条件。这些患者接受阿帕替尼治疗，每日剂量为 500 毫克口服，该药物被作为三线或更高线数药物使用。动态执行捕获测序以鉴定循环肿瘤 DNA (ctDNA) 中的体细胞变异体，其具有 1 021 个癌症相关的基因面板。主要终点为无进展生存期 (PFS) 以及根据实体瘤疗效评定标准 (RECIST) 1.1 版确定肿瘤反应。中期分析按预定义应用。
结果。2016 年 6 月 1 日至 2017 年 12 月 31 日共入组 26 例患者。全组中位 PFS 为 3.9 个月 [95% 置信区间(CI):2.1–5.9]。中位总生存期 (OS) 为 7.9 个月 (95% CI:4.6–10.1+)。体力状态 (PS) 为 0‐1 的患者的 PFS 较 PS 为 2 的患者长 (4.17 个月 vs. 1.93 个月，p = 0.001 4)。无肝转移患者的 PFS 也比肝转移患者长 (5.87 个月 vs. 3.33 个月，p = 0.027 4)。阿帕替尼的常见副作用是高血压、手足综合征、蛋白尿和腹泻。3–4 级高血压、手足综合征、蛋白尿、腹泻发生率分别为 76.92%、11.54%、73.08% 和 23.08%。所有患者均因不良反应减少了给药剂量。捕获测序结果显示，APC、TP53 和 KRAS 是最常见的突变基因。10 例患者在影像学检查前的ctDNA 丰度增加。
结论。阿帕替尼单一疗法对难治性结直肠癌疗效良好，尤其是对 PS 0‐1 或无肝转移患者。ctDNA 丰度可作为肿瘤负荷序列监测的预测因子。
© AlphaMed Press; the data published online to support this summary are the property of the authors.