Bevacizumab, Atezolizumab, and Acetylsalicylic Acid in Recurrent, Platinum-Resistant Ovarian Cancer: The EORTC 1508-GCG Phase II Study.

This phase II, randomized, multicentre trial evaluated the safety and activity of the anti-PD-L1 antibody atezolizumab (atezo) combined with the VEGF inhibitor bevacizumab (bev) and the irreversible cyclooxygenase 1/2 inhibitor aspirin [acetylsalicylic acid (ASA)] in PROC.

这项II期、随机、多中心试验评估了抗PD-L1抗体阿替利珠单抗（atezo）联合VEGF抑制剂贝伐珠单抗（bev）以及不可逆的环氧合酶1/2抑制剂阿司匹林[乙酰水杨酸（ASA）]在铂类耐药卵巢癌（PROC）中的安全性和活性。

patients_and_methods

Patients were randomized to bev monotherapy 15 mg/kg (arm 1), atezo 1,200 mg plus placebo (pbo; arm 2), atezo 1,200 mg plus ASA 320 mg/daily (arm 3), bev 15 mg/kg plus atezo 1,200 mg plus pbo (arm 4), or bev 15 mg/kg plus atezo 1,200 mg plus ASA 320 mg/daily (arm 5).

患者被随机分配到贝伐单抗单药治疗15 mg/kg（第1组），阿替利珠单抗1,200 mg加安慰剂（第2组），阿替利珠单抗1,200 mg加阿司匹林320 mg/日（第3组），贝伐单抗15 mg/kg加阿替利珠单抗1,200 mg加安慰剂（第4组），或贝伐单抗15 mg/kg加阿替利珠单抗1,200 mg加阿司匹林320 mg/日（第5组）。

Primary endpoint was progression-free survivalat 6 months (PFS-6) according to RECIST v1.1 assessed by a local investigator.

主要终点是根据RECIST v1.1评估的6个月无进展生存（PFS-6），由当地研究者进行评估。

Secondary objectives included overall survival, PFS, second PFS (PFS2), and tolerability.

次要研究终点包括总生存、无进展生存期（PFS）、第二次无进展生存期（PFS2）和耐受性。

Time to first subsequent therapy (TFST) was evaluated in a post hoc analysis.

首次后续治疗时间（TFST）在事后分析中进行了评估。

Results

In arms 1 (bev), 4 (bev-atezo-pbo), and 5 (bev-atezo-ASA), there were 7/32 [21.9%, 70% confidence interval(CI), 14.0-32.0], 8/32 (25.0%, 70% CI, 16.6-35.3), and 8/32 (25.0%, 70% CI, 16.6-35.3) patients alive and progression-free at 6 months.

在第1组（bev）、第4组（bev-atezo-pbo）和第5组（bev-atezo-ASA）中，分别有7/32（21.9%，70%置信区间（CI），14.0-32.0）、8/32（25.0%，70% CI，16.6-35.3）和8/32（25.0%，70% CI，16.6-35.3）的患者在6个月时仍然存活且无疾病进展。

The primary objective was not reached in any arm.

在任何一组中都没有达到主要研究终点。

Median PFS and response rates were 2.3 for bev monotherapy, 4.1 for bev-atezo-pbo, and 4.0 months for bev-atezo-ASA and 10%, 19%, and 15%, respectively.

中位无进展生存期（PFS）和反应率分别为贝伐单抗单药治疗的2.3个月和10%，贝伐单抗联合阿替佐米安慰剂组的4.1个月和19%，以及贝伐单抗联合阿替佐米和阿司匹林组的4.0个月和15%。

Two patients achieved an ongoing complete response lasting for more than 5 years from randomization (1 in bev-atezo-pbo and 1 in bev-atezo-ASA).

有两名患者实现了持续超过5年的完全缓解，从随机分组开始计算（1名在贝伐单抗联合阿替佐米安慰剂组，1名在贝伐单抗联合阿替佐米和阿司匹林组）。

A post hoc analysis of TFST suggested benefit of adding bev to atezo-ASA (P < 0.001).

TFST的事后分析表明，将bev添加到atezo-ASA中具有益处（P < 0.001）。

Tumor-infiltrating lymphocytes (TIL) increased in the atezo-containing arms after the first two cycles, and increased TIL were associated with a significantly longer TFST.

在前两个周期后，atezo组的肿瘤浸润淋巴细胞（TIL）增加，TIL的增加与TFST显著延长相关。

Conclusions

The addition of ASA to bev plus atezo was well-tolerated but did not improve efficacy in PROC.

将阿司匹林添加到贝伐单抗加阿替利珠单抗中耐受性良好，但在程序性细胞死亡中并未改善疗效。

Relative to bev alone, the bev plus atezo combination numerically improved PFS.

与单独使用贝伐单抗相比，贝伐单抗加阿替利珠单抗的组合在数值上改善了无进展生存期。

Exploratory translational analyses suggest clinical benefit in a subgroup of patients characterized by high TIL infiltration and PD-L1-positive tumors at baseline.

探索性转化分析表明，在基线时具有高TIL浸润和PD-L1阳性肿瘤特征的患者亚组中，临床获益显著。