Medical Oncology, Hôpital Européen Georges Pompidou, AP-HP Centre-Université Paris Cité, Paris, France.
INSERM U970, PARCC, Paris, France.
Int J Cancer. 2022 Oct 15;151(8):1335-1344. doi: 10.1002/ijc.34126. Epub 2022 Jun 6.
Nivolumab and cabozantinib are approved agents in mRCC patients after sunitinib/pazopanib (TKI) failure. However, the optimal sequence, cabozantinib then nivolumab (CN) or nivolumab then cabozantinib (NC), is still unknown. The CABIR study aimed to identify the optimal sequence between CN and NC after frontline VEGFR-TKI. In this multicenter retrospective study, we collected data from mRCC pts receiving CN or NC, after frontline VEGFR-TKI. A propensity score (PrS) was calculated to manage bias selection, and sequence comparisons were carried out with a cox model on a matched sample 1:1. The primary endpoint was progression-free survival (PFS) from the start of second line to progression in third line (PFS ). Key secondary endpoints included overall survival from second line (OS ). Out of 139 included mRCC patients, 38 (27%) and 101 (73%) received CN and NC, respectively. Overlap in PrS allowed 1:1 matching for each CN pts, with characteristics well balanced. For both PFS and OS , NC sequence was superior to CN (PFS : HR = 0.58 [0.34-0.98], P = .043; OS : 0.66 [0.42-1.05], P = .080). Superior PFS was in patients treated between 6 and 18 months with prior VEGFR-TKI (P = .019) and was driven by a higher PFS with cabozantinib when given after nivolumab (P < .001). The CABIR study shows a prolonged PFS of the NC sequence compared to CN in mRCC after first line VEGFR-TKI failure. The data suggest that cabozantinib may be more effective than nivolumab in the third-line setting, possibly related to an ability of cabozantinib to overcome resistance to PD-1 blockade.
纳武利尤单抗和卡博替尼已被批准用于舒尼替尼/帕唑帕尼(TKI)治疗失败后的 mRCC 患者。然而,CN 和 NC 两种方案的最佳顺序(先卡博替尼后纳武利尤单抗,CN;还是先纳武利尤单抗后卡博替尼,NC)仍不明确。CABIR 研究旨在明确一线 VEGFR-TKI 治疗后 CN 和 NC 两种方案的最佳顺序。在这项多中心回顾性研究中,我们收集了一线 VEGFR-TKI 治疗后接受 CN 或 NC 治疗的 mRCC 患者的数据。采用倾向评分(PrS)来管理选择偏倚,并在匹配样本 1:1 上采用 Cox 模型进行序列比较。主要终点为二线开始至三线进展的无进展生存期(PFS)。次要终点包括二线的总生存期(OS)。纳入的 139 例 mRCC 患者中,38 例(27%)和 101 例(73%)分别接受了 CN 和 NC。PrS 重叠允许对每个 CN 患者进行 1:1 匹配,特征均衡良好。CN 方案与 NC 方案相比,PFS 和 OS 均较差(PFS:HR=0.58[0.34-0.98],P=0.043;OS:0.66[0.42-1.05],P=0.080)。二线治疗中位时间为 6-18 个月的患者和一线 VEGFR-TKI 治疗后 6 个月内的患者,PFS 均优于 NC 方案(P=0.019),二线使用卡博替尼优于纳武利尤单抗,且具有统计学意义(P<0.001)。CABIR 研究表明,一线 VEGFR-TKI 治疗失败后,mRCC 患者接受 NC 方案的 PFS 较 CN 方案延长。数据表明,卡博替尼在三线治疗中的疗效可能优于纳武利尤单抗,这可能与卡博替尼克服 PD-1 阻断耐药的能力有关。
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