Comparing Durvalumab, Olaparib, and Cediranib Monotherapy, Combination Therapy, or Chemotherapy in Patients with Platinum-Resistant Ovarian Cancer with Prior Bevacizumab: The Phase II NRG-GY023 Trial.

patients_and_methods

NRG-GY023 was the first randomized four-arm superiority phase II trial enrolling patients with high-grade serous/endometrioid or clear-cell PROC with prior bevacizumab exposure.

NRG-GY023是首个随机四臂优势性II期试验，招募了既往接受过贝伐单抗治疗的高级别浆液性/子宫内膜样或透明细胞型PROC患者。

Patients were randomized 1:2:2:2 to SOC (weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin), DOC, durvalumab + cediranib (DC), or olaparib + cediranib (OC).

患者按1:2:2:2的比例随机分配到SOC（每周紫杉醇、托泊替康或聚乙二醇化脂质体多柔比星）、DOC、durvalumab + cediranib（DC）或olaparib + cediranib（OC）治疗组。

The primary endpoint was progression-free survival(PFS).

主要终点是无进展生存（PFS）。

The secondary endpoints included overall survival, overall response rate, and safety.

次要终点包括总生存、总体反应率和安全性。

The design had 80% power to detect an HR of 0.5 using a one-sided, α = 0.1-level test for each comparison with the SOC with a preplanned interim analysis.

该设计具有80%的把握度，使用单侧、α=0.1水平的检验，计划在事前进行中期分析，以检测与标准治疗相比的HR为0.5。

Experimental arms with HR estimates (vs. SOC) >0.87 could be discontinued.

与标准治疗（SOC）相比，风险比（HR）估计值>0.87的实验组可以被终止。

Results

A total of 153 patients were enrolled between April 4, 2021, and February 1, 2023.

2021年4月4日至2023年2月1日期间，共有153名患者被纳入研究。

Accrual was permanently closed on February 1, 2023, due to futility.

由于无效性，招募工作已于2023年2月1日永久关闭。

With a data cutoff of September 9, 2024, the median PFS was 3.4, 2.9, 2.5, and 2.8 months, and median overall survivalwas 7.5, 8.3, 5.7, and 10.2 months for SOC, DOC, DC, and OC, respectively.

截至2024年9月9日的数据截止日期，标准治疗（SOC）、实验治疗（DOC）、双药联合治疗（DC）和单药治疗（OC）的中位无进展生存期（PFS）分别为3.4个月、2.9个月、2.5个月和2.8个月；中位总生存期（OS）分别为7.5个月、8.3个月、5.7个月和10.2个月。

The overall response rate was 4.3% [95% confidence interval(CI), 0.00-0.19], 15.9% (95% CI, 0.07-0.29), 11.9% (95% CI, 0.05-0.24), and 9.1% (95% CI, 0.03-0.20) for SOC, DOC, DC, and OC, respectively.

总反应率分别为标准治疗组（SOC）4.3%（95%置信区间（CI），0.00-0.19），去氧胆酸组（DOC）15.9%（95% CI，0.07-0.29），二氯组（DC）11.9%（95% CI，0.05-0.24），以及奥沙利铂组（OC）9.1%（95% CI，0.03-0.20）。

Compared with SOC, the PFS HR estimates were 1.003 (95% CI, 0.56-1.80), 1.108 (95% CI, 0.63-1.96), and 1.021 (95% CI, 0.57-1.82) for DOC, DC, and OC, respectively.

与SOC相比，无进展生存期（PFS）风险比（HR）估计值分别为DOC 1.003（95% CI，0.56-1.80），DC 1.108（95% CI，0.63-1.96），以及OC 1.021（95% CI，0.57-1.82）。

No new safety signals were observed.

未观察到新的安全信号。

Conclusions

In patients with PROC with prior bevacizumab, all experimental arms failed to reach the primary objective of improving PFS compared with SOC.

在先前接受过贝伐珠单抗治疗的PROC患者中，所有实验组均未能达到改善无进展生存期（PFS）的主要研究目标，与标准治疗（SOC）相比。