Department of Medical Oncology, Ankara University School of Medicine, Ankara, Türkiye; Ankara University Cancer Research Institute, Ankara, Türkiye.
Ankara Etlik City Hospital, Medical Oncology Clinic, Ankara, Türkiye.
Cancer Treat Rev. 2024 Jan;122:102667. doi: 10.1016/j.ctrv.2023.102667. Epub 2023 Dec 10.
Immunotherapy (IO)-based combination therapies have emerged as the standard of care for first-line treatment of metastatic renal cell carcinoma (mRCC) among patients classified as intermediate and poor risk. However, in the favorable risk group, the available data remains less compelling. This study aims to assess and compare the effectiveness of IO-based combination therapies versus tyrosine kinase inhibitor (TKI) monotherapy in patients with favorable risk group according to the International mRCC Database Consortium (IMDC).
Recent update data from phase-III RCTs of IO-based combinations approved by the Food and Drug Administration were used. Studies that provided data on progression free survival (PFS) and overall survival (OS) of IMDC favorable risk were included in the analysis.
A cohort of 1,088 patients categorized within the IMDC favorable risk group was enrolled for analysis. In comparison to sunitinib, the combination of immunotherapy (IO) and tyrosine kinase inhibitor (TKI) exhibited a reduction in the risk of disease progression (HR = 0.67, 95 % CI: 0.55-0.82; p < 0.001). Conversely, the combination of IO and IO displayed an elevated risk of disease progression (HR = 1.60, 95 % CI: 1.13-2.26; p = 0.008). However, neither the IO plus TKI (HR = 0.99, 95 % CI: 0.79-1.24; p = 0.92) nor IO plus IO (HR = 0.94, 95 % CI: 0.64-1.37; p = 0.75) combinations demonstrated a noteworthy improvement in overall survival (OS). Notably, within the IO plus TKI subgroup, combination therapy yielded a higher objective response rate (ORR) (OR = 0.40, 95 % CI: 0.28-0.57; p < 0.001). On the other hand, the IO plus IO combination displayed a lower ORR than sunitinib (OR = 2.54, 95 % CI: 1.51-4.27; p < 0.001).
In the first-line treatment of IMDC favorable-risk mRCC, IO and TKI combinations show enhanced progression-free survival and response rate without improving overall survival. This emphasizes the demand for further exploration of combination therapies in this patient group.
免疫疗法（IO）为基础的联合疗法已经成为转移性肾细胞癌（mRCC）中中危和高危患者一线治疗的标准。然而，在低危患者中，目前的数据仍然不太令人信服。本研究旨在根据国际 mRCC 数据库联盟（IMDC）评估和比较 IO 为基础的联合治疗与酪氨酸激酶抑制剂（TKI）单药治疗低危患者的疗效。
使用美国食品和药物管理局批准的基于 IO 的联合治疗的 III 期 RCT 的最新更新数据。对纳入的 IMDC 低危风险患者进行无进展生存期（PFS）和总生存期（OS）分析。
共纳入 1088 例 IMDC 低危风险患者。与舒尼替尼相比，IO 联合 TKI 治疗降低了疾病进展风险（HR=0.67，95%CI：0.55-0.82；p<0.001）。相反，IO 联合 IO 治疗增加了疾病进展风险（HR=1.60，95%CI：1.13-2.26；p=0.008）。然而，IO 联合 TKI（HR=0.99，95%CI：0.79-1.24；p=0.92）或 IO 联合 IO（HR=0.94，95%CI：0.64-1.37；p=0.75）均未显著改善总生存期（OS）。值得注意的是，在 IO 联合 TKI 亚组中，联合治疗的客观缓解率（ORR）更高（OR=0.40，95%CI：0.28-0.57；p<0.001）。另一方面，IO 联合 IO 的 ORR 低于舒尼替尼（OR=2.54，95%CI：1.51-4.27；p<0.001）。
在 IMDC 低危 mRCC 的一线治疗中，IO 和 TKI 联合治疗可提高无进展生存期和缓解率，而不改善总生存期。这强调了在该患者群体中进一步探索联合治疗的必要性。
