阿昔替尼单药或联合帕博利珠单抗治疗舒尼替尼治疗失败的伴肝转移肾细胞癌的疗效及安全性分析

目的 研究阿昔替尼单药或联合帕博利珠单抗治疗舒尼替尼治疗失败的伴肝转移肾细胞癌的疗效及安全性。方法 选取2018年1月—2020年5月南京医科大学第二附属医院和南京医科大学第四附属医院收治的26例肾细胞癌患者为研究对象。对照组13例接受阿昔替尼单药口服治疗，观察组13例接受阿昔替尼口服联合帕博利珠单抗治疗，比较两组患者的临床疗效、生活质量、免疫功能、血清肿瘤标志物水平及毒副反应发生率。结果 治疗后，观察组客观缓解率（61.5%）显著高于对照组（30.8%）（P<0.05）；观察组生活质量较对照组略有下降，但差异无统计学意义（P>0.05）；两组患者血清肿瘤标志物CEA、Cyfra21-1、CA125水平均较治疗前明显下降（P<0.05），且观察组血清CEA、Cyfra21-1水平显著低于对照组（P<0.05）；观察组免疫功能指标CD3⁺、CD8⁺、NK细胞水平均显著高于对照组（P<0.05）；观察组患者白细胞减少、血小板减少、甲状腺功能异常、肝功能损害、胃肠道反应、皮疹、乳酸脱氢酶升高等不良反应发生率均高于对照组，除皮疹外，两组其余不良反应的发生率比较，差异均具有统计学意义（P<0.05）。结论 阿昔替尼单药或联合帕博利珠单抗均能为舒尼替尼治疗失败的伴肝转移肾细胞癌患者带来疗效获益，且联合帕博利珠单抗的疗效和免疫功能获益均显著优于单药治疗，但联合免疫检查点抑制剂也造成了不良反应的显著增加。

Efficacy and safety of axitinib single agent or combined with pembrolizumab in the treatment of renal cell carcinoma with liver metastases after failure in sunitinib treatment

Objective To investigate the clinical efficacy of axitinib single agent or combined with pembrolizumab in the treatment of renal cell carcinoma with liver metastases that failed in sunitinib treatment.Methods Twenty-six patients with renal cell carcinoma admitted to the Second Affiliated Hospital of Nanjing Medical University and the Fourth Affiliated Hospital of Nanjing Medical University between January 2018 and May 2020 were selected in this study. The control group received oral axitinib single agent, and the observation group received oral axitinib combined with pembrolizumab. The clinical efficacy, quality of life, improvement of immune function, serum levels of tumor markers and incidence of side effects were compared between the two groups.Results After treatment, the objective response rate was higher in the observation group (61.5%) than in the control group (30.8%) (P<0.05). The quality of life score of the observation group was slightly lower than that of the control group, but the difference was not statistically significant (P>0.05). After treatment, the serum levels of tumor markers CEA, Cyfra21-1 and CA125 of patients in the two groups were significantly lower than before treatment (P<0.05). In addition, the serum levels of tumor markers CEA and Cyfra21-1 in the observation group were statistically lower than those of the control group after treatment (P<0.05). The main immune indexes CD3⁺, CD8⁺ and NK cell activity of the observation group were significantly higher than those of the control group (P<0.05). The incidence rates of adverse reactions in the observation group, including leukopenia, thrombocytopenia, abnormal thyroid function, liver damage, gastrointestinal reactions, rash and rise of lactate dehydrogenase, were all higher than those of the control group. The differences were statistically significant between the two groups except for that of rash (P<0.05).Conclusion Axitinib alone or in combination with pembrolizumab can bring curative benefits to renal cell carcinoma patients with liver metastases after failure in sunitinib treatment. Axitinib in combination with pembrolizumab showed greater efficacy and immune function benefits than axitinib alone, but brought a significant increase in the occurrence of adverse reactions.