We describe results from IMmotion150, a randomized phase 2 study of atezolizumab (anti-PD-L1) alone or combined with bevacizumab (anti-VEGF) versus sunitinib in 305 patients with treatment-naive metastatic renal cell carcinoma. Co-primary endpoints were progression-free survival (PFS) in intent-to-treat and PD-L1+ populations. Intent-to-treat PFS hazard ratios for atezolizumab + bevacizumab or atezolizumab monotherapy versus sunitinib were 1.0 (95% confidence interval (CI), 0.69-1.45) and 1.19 (95% CI, 0.82-1.71), respectively; PD-L1+ PFS hazard ratios were 0.64 (95% CI, 0.38-1.08) and 1.03 (95% CI, 0.63-1.67), respectively. Exploratory biomarker analyses indicated that tumor mutation and neoantigen burden were not associated with PFS. Angiogenesis, T-effector/IFN-γ response, and myeloid inflammatory gene expression signatures were strongly and differentially associated with PFS within and across the treatments. These molecular profiles suggest that prediction of outcomes with anti-VEGF and immunotherapy may be possible and offer mechanistic insights into how blocking VEGF may overcome resistance to immune checkpoint blockade.

中文翻译：

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肾细胞癌中单独或与贝伐单抗联合舒尼替尼联合使用对阿特珠单抗的临床活性和分子相关性。

我们描述了IMmotion150的结果，这是305例初治转移性肾癌患者中单独使用atezolizumab（抗PD-L1）或与贝伐单抗（抗VEGF）联合舒尼替尼治疗的2期随机研究。共同主要终点是意图治疗人群和PD-L1 +人群的无进展生存期（PFS）。Atezolizumab + Bevacizumab或Atezolizumab单药治疗与舒尼替尼的意向治疗PFS危险比分别为1.0（95％置信区间（CI），0.69-1.45）和1.19（95％CI，0.82-1.71）; PD-L1 + PFS危险比分别为0.64（95％CI，0.38-1.08）和1.03（95％CI，0.63-1.67）。探索性生物标志物分析表明，肿瘤突变和新抗原负担与PFS无关。血管生成，T效应子/IFN-γ反应，在治疗过程中和治疗过程中，PFS和骨髓炎性基因表达特征均与PFS密切相关。这些分子特征表明，用抗VEGF和免疫疗法对结果进行预测可能是可能的，并为阻断VEGF如何克服对免疫检查点阻断的抗性提供了机械方面的见解。