Department of Urology, Tokyo Women's Medical University, 8-1 Kawada-Cho, Shinjuku-Ku, Tokyo, Japan.
Department of Innovative Research and Education for Clinicians and Trainees (DiRECT), Fukushima Medical University Hospital, 1 Hikarigaoka, Fukushima, Fukushima, Japan.
Int J Clin Oncol. 2024 Apr;29(4):473-480. doi: 10.1007/s10147-024-02471-w. Epub 2024 Feb 12.
There are few comparative studies on dual immune checkpoint inhibitors (ICIs) (i.e., IO-IO) and combination therapies comprising ICIs plus tyrosine kinase inhibitors (TKIs) (i.e., IO-TKI) for advanced renal cell carcinoma (RCC), especially in real-world settings.
We retrospectively evaluated data of 175 patients with IMDC intermediate-risk or poor-risk RCC; as first-line therapy, 103 received IO-IO, and 72 received IO-TKI. An inverse probability of treatment weighting (IPTW) analysis was conducted to balance patients' backgrounds in the IO-IO and IO-TKI groups.
Based on the IPTW analysis, progression-free survival (PFS) was longer in the IO-TKI group than in the IO-IO group (median: 15.6 vs. 8.3 months; p = 0.0386). In contrast, overall survival was not different between groups (median: 46.7 vs. 49.0 months; p = 0.465). Although the IPTW-adjusted objective response rate was not significantly different (51.2% vs. 43.9%; p = 0.359), the progressive disease rate as the best overall response was lower in the IO-TKI group than in the IO-IO group (3.3% vs. 27.4%; p < 0.0001). Regarding the safety profile, the treatment interruption rate was higher in the IO-TKI group than in the IO-IO group (70.3% vs. 49.2%; p = 0.005). In contrast, the IO-IO group had a higher corticosteroid administration rate (43.3% vs. 20.3%; p = 0.001).
IO-TKI therapy exhibited superior effectiveness over IO-IO therapy in terms of PFS improvement and immediate disease progression prevention and was associated with a higher risk of treatment interruption and a lower risk of needing corticosteroids.
在晚期肾细胞癌(RCC)的治疗中,针对双重免疫检查点抑制剂(ICI)(即 IO-IO)与包含 ICI 加酪氨酸激酶抑制剂(TKI)的联合疗法(即 IO-TKI),目前仅有为数不多的比较研究,特别是在真实世界环境中。
我们回顾性评估了 175 例国际转移性肾细胞癌数据库联盟(IMDC)中危或高危 RCC 患者的数据;作为一线治疗,103 例患者接受 IO-IO,72 例患者接受 IO-TKI。采用逆概率治疗加权(IPTW)分析平衡 IO-IO 和 IO-TKI 两组患者的背景。
基于 IPTW 分析,IO-TKI 组的无进展生存期(PFS)长于 IO-IO 组(中位数:15.6 个月 vs. 8.3 个月;p=0.0386)。相反,两组的总生存期无差异(中位数:46.7 个月 vs. 49.0 个月;p=0.465)。虽然 IPTW 调整后的客观缓解率无显著差异(51.2% vs. 43.9%;p=0.359),但 IO-TKI 组的最佳总体反应进展疾病率低于 IO-IO 组(3.3% vs. 27.4%;p<0.0001)。关于安全性概况,IO-TKI 组的治疗中断率高于 IO-IO 组(70.3% vs. 49.2%;p=0.005)。相反,IO-IO 组的皮质类固醇使用率较高(43.3% vs. 20.3%;p=0.001)。
与 IO-IO 治疗相比,IO-TKI 治疗在改善 PFS 和立即预防疾病进展方面表现出更好的疗效,且与更高的治疗中断风险和更低的皮质类固醇需求相关。