免疫联合靶向二线治疗转移性非透明细胞肾细胞癌的疗效及安全性

Efficacy and safety evaluation of immunotherapy combined with targeted therapy as second-line treatment in patients with metastatic non-clear cell renal cell carcinoma

目的评估程序性死亡蛋白1(PD-1)抑制剂联合酪氨酸激酶抑制剂(TKI)作为TKI一线治疗失败的转移性非透明细胞肾癌(nccRCC)二线治疗方案的临床疗效及安全性。方法回顾性分析2011年10月至2020年9月在中山大学肿瘤防治中心接受TKI一线治疗后进展的67例转移性nccRCC患者的临床病理资料。根据二线治疗方案,将患者分为TKI单药治疗组(22例)和免疫联合靶向治疗组(45例),TKI单药治疗组患者接受TKI单药二线治疗,免疫联合靶向治疗组患者接受TKI联合PD-1抑制剂的二线治疗。采用实体瘤的疗效评价标准(RECIST)1.0/1.1进行疗效评估,采用Kaplan-Meier法进行生存分析,并观察两组患者的治疗相关不良反应。结果全部67例患者的客观缓解率(ORR)为37.3%(25/67),疾病控制率(DCR)为56.7%(38/67),二线治疗后的中位无进展生存时间(PFS)为7.7个月,中位总生存时间(OS)为25.2个月。免疫联合靶向治疗组患者的ORR为48.9%(22/45),DCR为71.1%(32/45),与TKI单药治疗组[分别为13.6%(3/22)和27.3%(6/22)]相比明显改善(P值分别为0.007和0.001)。免疫联合靶向治疗组患者二线治疗的中位PFS为9.2个月,长于TKI单药治疗组(5.2个月,P=0.001),但中位OS(28.2个月)与TKI单药治疗组(20.8个月)差异无统计学意义(P=0.068)。两组常见的治疗相关不良反应包括高血压、腹泻、乏力、口腔炎、手足综合征和甲状腺功能减退。免疫联合靶向治疗组甲状腺功能减退的发生率[40.0%(18/45)]高于TKI单药治疗组[22.7%(5/22),P=0.044],除此之外,两组间其他治疗相关不良反应的发生率差异均无统计学意义(均P>0.05)。结论对TKI一线治疗失败的转移性nccRCC,免疫联合靶向治疗比单一靶向治疗更有效,且患者的耐受性良好。

Objective This study aimed to evaluate the efficacy and safety of programmed death-1(PD-1)inhibitor combined tyrosine kinase inhibitor(TKI)therapy versus TKI monotherapy as the second-line regimen for patients with metastatic non-clear cell renal carcinoma(nccRCC)who failed first-line TKI therapy.Methods The clinicopathological data of 67 patients with metastatic nccRCC who failed first-line TKI therapy between October 2011 and September 2020 were retrospectively analyzed,including 22 patients who received TKI monotherapy and 45 patients who received TKI plus PD-1 inhibitor as the second-line therapy.The efficacy was assessed according to Response Evaluation Criteria in Solid Tumors version 1.0/1.1(RECIST 1.0/1.1),the Kaplan-Meier method was used to plot the survival curves,and the Log rank test was used to analyze the differences in the survival between the two groups.Treatment-related adverse events(AEs)after treatment were observed in both groups.Results The overall objective response rate(ORR)and disease control rate(DCR)were 37.3%(25/67)and 56.7%(38/67),respectively.The overall second-line progression-free survival(PFS)was 7.7 months and Overall Survival(OS)was 25.2 months.The ORR and DCR of patients in the combination therapy group were 48.9%(22/45)and 71.1%(32/45),respectively,which were significantly improved compared with the TKI monotherapy group[13.6%(3/22)and 27.3%(6/22),respectively](P=0.007 and P=0.001,respectively).The median PFS of 9.2 months for second-line treatment was longer in patients in the combination therapy group than in the TKI monotherapy group(5.2 months,P=0.001),but the median OS was not statistically different between the two groups(28.2 months vs 20.8 months,P=0.068).Common treatment-related AEs included hypertension,diarrhea,fatigue,stomatitis,hand-foot syndrome,and hypothyroidism.The incidence of hypothyroidism was higher in the combination therapy group[40.0%(18/45)]than in the TKI monotherapy group[22.7%(5/22),P=0.044];the incidence of other treatment-related AEs between the two groups were not statistically significant(all P>0.05).Conclusion Immune-targeted combination therapy was more effective than TKI monotherapy alone and was well tolerated in the treatment of metastatic nccRCC patients who failed first-line TKIs.