免疫检查点抑制剂双重联合疗法与免疫检查点抑制剂加酪氨酸激酶抑制剂联合疗法对晚期肾细胞癌患者免疫相关不良事件影响的比较
Comparison of the Impact of Immune-Related Adverse Events Due to Immune Checkpoint Inhibitor Dual Combination Therapy and Immune Checkpoint Inhibitor Plus Tyrosine Kinase Inhibitor Combination Therapy in Patients with Advanced Renal Cell Carcinoma.
作者信息
Ishihara Hiroki, Nemoto Yuki, Nakamura Kazutaka, Tachibana Hidekazu, Fukuda Hironori, Yoshida Kazuhiko, Kobayashi Hirohito, Iizuka Junpei, Shimmura Hiroaki, Hashimoto Yasunobu, Kondo Tsunenori, Takagi Toshio
机构信息
Department of Urology, Tokyo Women's Medical University Adachi Medical Center, 4-33-1 Kouhoku, Adachi-ku, Tokyo, Japan.
Department of Urology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, Japan.
出版信息
Target Oncol. 2023 Jan;18(1):159-168. doi: 10.1007/s11523-022-00940-8. Epub 2022 Dec 26.
BACKGROUND
The prognostic impact of immune-related adverse events during immune checkpoint inhibitor-based combination therapy for advanced renal cell carcinoma remains unclear, especially in terms of differences between regimens.
OBJECTIVE
We aimed to clarify the prognostic impact of immune-related adverse events in patients with advanced renal cell carcinoma receiving immune checkpoint inhibitor dual combination therapy (IO-IO) or immune checkpoint inhibitor plus tyrosine kinase inhibitor combination therapy (IO-TKI).
METHODS
We retrospectively evaluated the data of 148 patients who received immune checkpoint inhibitor-based combination therapy as first-line therapy. Patients were divided into two groups based on regimens, namely IO-IO and IO-TKI. The associations between immune-related adverse event development and outcomes, such as progression-free survival, overall survival, and objective response rate, were compared between the two groups.
RESULTS
In the IO-IO and IO-TKI groups, 67 of 91 (74%) and 31 of 57 (54%) patients, respectively, experienced at least one immune-related adverse event and the rate was significantly higher in the IO-IO group (p = 0.0204), where immune-related adverse events development was significantly associated with longer progression-free survival (p < 0.0001) and overall survival (p = 0.0102), and a higher objective response rate (p = 0.0028). A multivariate analysis revealed immune-related adverse event development as an independent factor for longer progression-free survival (hazard ratio, 0.25; p < 0.0001) and overall survival (hazard ratio, 0.42; p = 0.0287). There were no significant associations between immune-related adverse events and progression-free survival, overall survival, or objective response rate in the IO-TKI group.
CONCLUSIONS
The development of immune-related adverse events was positively associated with the outcome of patients with advanced renal cell carcinoma treated with IO-IO combination therapy; no such correlation was observed for IO-TKI combination therapy.
背景
在基于免疫检查点抑制剂的晚期肾细胞癌联合治疗中，免疫相关不良事件的预后影响仍不明确，尤其是不同治疗方案之间的差异。
目的
我们旨在阐明免疫相关不良事件对接受免疫检查点抑制剂双联联合治疗（IO-IO）或免疫检查点抑制剂加酪氨酸激酶抑制剂联合治疗（IO-TKI）的晚期肾细胞癌患者的预后影响。
方法
我们回顾性评估了148例接受基于免疫检查点抑制剂联合治疗作为一线治疗的患者的数据。根据治疗方案将患者分为两组，即IO-IO组和IO-TKI组。比较两组免疫相关不良事件的发生与无进展生存期、总生存期和客观缓解率等结局之间的关联。
结果
在IO-IO组和IO-TKI组中，分别有91例中的67例（74%）和57例中的31例（54%）患者经历了至少一次免疫相关不良事件，IO-IO组的发生率显著更高（p = 0.0204），在该组中免疫相关不良事件的发生与更长的无进展生存期（p < 0.0001）、总生存期（p = 0.0102）以及更高的客观缓解率（p = 0.0028）显著相关。多因素分析显示免疫相关不良事件的发生是更长无进展生存期（风险比，0.25；p < 0.0001）和总生存期（风险比，0.42；p = 0.0287）的独立因素。在IO-TKI组中，免疫相关不良事件与无进展生存期、总生存期或客观缓解率之间无显著关联。
结论
免疫相关不良事件的发生与接受IO-IO联合治疗的晚期肾细胞癌患者的结局呈正相关；IO-TKI联合治疗未观察到这种相关性。
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