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.
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。.
Zhonghua zhong liu za zhi [Chinese journal of oncology]. 2023 Aug 23 [Epub]
J Wang, W S Wei, L J Jiang, Z L Zhang, S J Guo, H Han, F J Zhou, P Dong
Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.