Wang J, Wei W S, Jiang L J, Zhang Z L, Guo S J, Han H, Zhou F J, Dong P
Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Zhonghua Zhong Liu Za Zhi. 2023 Aug 23;45(8):704-708. doi: 10.3760/cma.j.cn112152-20220330-00220.
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. 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. 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] (=0.007 and =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, =0.001), but the median OS was not statistically different between the two groups (28.2 months vs 20.8 months, =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), =0.044]; the incidence of other treatment-related AEs between the two groups were not statistically significant (all >0.05). 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.
本研究旨在评估程序性死亡-1（PD-1）抑制剂联合酪氨酸激酶抑制剂（TKI）治疗与TKI单药治疗作为一线TKI治疗失败的转移性非透明细胞肾细胞癌（nccRCC）患者二线治疗方案的疗效和安全性。回顾性分析了2011年10月至2020年9月期间67例一线TKI治疗失败的转移性nccRCC患者的临床病理资料，其中22例接受TKI单药治疗，45例接受TKI联合PD-1抑制剂作为二线治疗。根据实体瘤疗效评价标准1.0/1.1版（RECIST 1.0/1.1）评估疗效，采用Kaplan-Meier法绘制生存曲线，采用Log rank检验分析两组生存差异。观察两组治疗后与治疗相关的不良事件（AE）。总客观缓解率（ORR）和疾病控制率（DCR）分别为37.3%（25/67）和56.7%（38/67）。二线总无进展生存期（PFS）为7.7个月，总生存期（OS）为25.2个月。联合治疗组患者的ORR和DCR分别为48.9%（22/45）和71.1%（32/45），与TKI单药治疗组[分别为13.6%（3/22）和27.3%（6/22）]相比有显著改善（分别为=0.007和=0.001）。联合治疗组二线治疗的中位PFS为9.2个月，长于TKI单药治疗组（5.2个月，=0.001），但两组中位OS无统计学差异（28.2个月对20.8个月，=0.068）。常见的治疗相关AE包括高血压、腹泻、疲劳、口腔炎、手足综合征和甲状腺功能减退。联合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），=0.044]；两组其他治疗相关AE的发生率无统计学差异（均>0.05）。免疫靶向联合治疗比单独使用TKI单药治疗更有效，并且在一线TKI治疗失败的转移性nccRCC患者治疗中耐受性良好。
