作者：李瑞华，邢现菲，刘亚萌，韩正全

单位：蚌埠医学院第一附属医院 肿瘤内科，安徽 蚌埠 233004

Authors:  Li Ruihua, Xing Xianfei, Liu Yameng, Han Zhengquan

Unit: Department of Oncology, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, Anhui, China

摘要：

目的 分析程序性死亡蛋白-1（PD-1）抑制剂联合呋喹替尼治疗晚期结直肠癌患者的临床疗效及安全性。方法 回顾性收集2021年1月至2022年12月间，蚌埠医学院第一附属医院收治的60例晚期微卫星稳定型（MSS）结直肠癌患者。根据治疗方案，将患者分为观察组和对照组，每组30例。对照组单用呋喹替尼，观察组在对照组基础上联合PD-1抑制剂。两组患者在完成2个治疗周期后，根据RECIST 1.1 版实体瘤评价标准进行评估。分析并比较两组患者在临床疗效、生活质量评分（KPS）以及不良反应方面的差异。结果 截至末次随访时间，观察组患者的客观缓解率（ORR）优于对照组（16.67%比6.67%，P=0.424）, 但差异无统计学意义。两组患者的疾病控制率（DCR）分别为66.67%和40.00%（P=0.038），差异具有统计学意义。在肝转移患者的亚组中，观察组和对照组肝转移患者的ORR 分别为9.52% 和5.56%，DCR 分别为57.14%和22.22%（P=0.049)。治疗后两组患者的KPS 得到明显改善，观察组明显高于对照组（P<0.05）。Kaplan-Meier 生存分析结果显示院与对照组相比，观察组的中位无进展生存（PFS）期更长（4.3个月比2.8个月，P<0.05）。在所有级别的不良反应中，观察组中最常见的药物不良反应为肝功能损害，其次为掌趾红肿综合征、高血压、蛋白尿、疲劳。对照组患者发生常见的药物不良反应依次为肝功能损害、高血压、掌趾红肿综合征、蛋白尿。两组患者的不良反应率比较，差异无统计学意义。结论 PD-1 抑制剂联合呋喹替尼可改善晚期MSS的CRC患者的DCR的PFS，且不良反应可控。

关键词： 结直肠癌；微卫星稳定型；程序性死亡蛋白-1；呋喹替尼；疗效；不良反应

Abstract：

Objective  The objective of this study was to evaluate the therapeutic effectiveness and safety of utilizing furoquinitinib in conjunction with programmed death receptor -1 (PD-1) inhibitors for treating patients with advanced colorectal cancer. Method Researchers gathered information on sixty patients with advanced MSS colorectal cancer who had treatment at a particular institution during a two-year period for this study. Then, with 30 patients in each group, the patients were split into two groups: an observation group and a control group. The observation group received a combination of PD-1 inhibitor and furoquinitinib while the control group received only furoquinitinib as treatment. After completing two treatment cycles, both groups were evaluated using the RECIST version 1.1 solid tumor evaluation criteria. The purpose of the study was to contrast the clinical effectiveness, KPS ratings, and side effects between the two groups. Result As of the most recent follow-up period, the objective response rate (ORR) of patients receiving PD-1 inhibitor combo therapy was greater than that of the control group (16.67% vs. 6.67%, P=0.424), while there was no statistically significant difference between the two groups. The disease control rate (DCR) differed statistically between groups (66.67% vs. 40.00% , P =0.038). The ORR of patients with liver metastases was 9.52% in the observation group and 5.56% in the control group, respectively, and the DCR was (57.14% vs. 22.22%, P=0.049) in the subgroup of patients with hepatic metastases. The KPS of patients in both groups improved significantly after treatment, and the observation group was significantly higher than the control group (P<0.05). According to the Kaplan-Meier survival analysis, the observation group had a longer median progression-free survival (PFS) than the control group (4.3 months vs. 2.8 months, P<0.05). Hepatic impairment was the most prevalent adverse medication reaction across all severity levels in the observation group, followed by palmar toe erythema syndrome, hypertension, proteinuria, and weariness. Hepatic impairment, hypertension, palmar toe erythema syndrome, and proteinuria were the most frequent adverse medication responses in the control group, going in that order. Between the two groups, there was no statistically significant difference in the incidence of negative reactions. Conclusion PD -1 inhibitor in combination with furoquinitinib improved DCR and PFS in patients with advanced MSS -type CRC with manageable adverse effects.

Key Words:  Colorectal cancer; Microsatellite stable; Programmed death receptor -1; Furoquinitinib; Efficacy; Adverse effects