Cabozantinib plus nivolumab and ipilimumab in previously untreated, advanced renal cell carcinoma: final results and biomarker analyses from the phase III COSMIC-313 study.

Final efficacy and safety results, as well as data from exploratory biomarker analyses, are reported here.

这里报告了COSMIC-313研究的最终疗效和安全性结果，以及探索性生物标志物分析的数据。

patients_and_methods

The design, participants, and primary-endpoint PFS outcomes have been reported previously for this phase III, double-blind, randomized (1 : 1) study of cabozantinib or placebo plus nivolumab and ipilimumab in adults with previously untreated, advanced clear cell renal cell carcinoma.

这项III期、双盲、随机（1:1）研究，涉及卡博佐替尼或安慰剂联合纳武利尤单抗和伊匹木单抗治疗先前未接受治疗的晚期透明细胞肾细胞癌成年患者，之前已经报告了设计、参与者和主要终点无进展生存期（PFS）的结果。

The secondary endpoint was overall survival(OS) in the intention-to-treatpopulation.

次要终点是在意向治疗人群中总生存（OS）。

Exploratory biomarker analyses investigated the potential association between immune cell types and gene signatures with clinical outcomes.

探索性生物标志物分析研究了免疫细胞类型和基因特征与临床结果之间的潜在关联。

Results

After a median follow-up of 45.0 months, the updated median PFS in the cabozantinib (triplet) arm was longer than in the placebo (doublet) arm (16.6 versus 11.2 months; hazard ratio0.82, 95% confidence interval0.69-0.98).

中位随访45.0个月后，更新的无进展生存期（PFS）中位数在卡博佐替尼（三联）组中比安慰剂（双联）组更长（16.6个月对比11.2个月；风险比0.82，95%置信区间0.69-0.98）。

There was no significant difference in median OS (hazard ratio1.02, 95% confidence interval0.85-1.23, P = 0.84), and the safety profile was consistent with the earlier analysis (grade 3/4 treatment-related adverse events occurred in 75% and 43% of patients in the triplet and doublet arms, respectively).

中位总生存期（风险比1.02，95%置信区间0.85-1.23，P = 0.84）没有显著差异，安全性与早期分析一致（三药方案组和双药方案组分别有75%和43%的患者出现3/4级治疗相关不良事件）。

In patients with higher levels of M2-like macrophages, the triplet regimen was associated with significantly improved PFS and OS compared with the doublet regimen.

在M2样巨噬细胞水平较高的患者中，三药方案与双药方案相比，无进展生存期（PFS）和总生存期（OS）显著改善。

Responders in the triplet arm exhibited elevated angiogenic signatures and reduced immune-related pathways, while responders in the doublet arm had robust immune activation.

三联疗法组的应答者表现出增强的血管生成特征和减少的免疫相关通路，而双联疗法组的应答者则显示出强烈的免疫激活。

Conclusions

Long-term results from COSMIC-313 continue to demonstrate a PFS benefit with the addition of cabozantinib to nivolumab and ipilimumab.

COSMIC-313的长期结果继续证明，将卡博替尼添加到纳武利尤单抗和伊匹木单抗中，可以带来无进展生存期（PFS）的益处。

There was no OS benefit and no new safety signals were observed.

未观察到总生存获益，也未发现新的安全信号。

Exploratory biomarker analyses suggest adding cabozantinib to nivolumab and ipilimumab improves survival in patients with high levels of M2-like macrophages.

探索性生物标志物分析表明，将卡博替尼与纳武利尤单抗和伊匹木单抗联合使用，可改善具有高水平M2样巨噬细胞患者的生存期。