在先前接受贝伐单抗治疗的铂耐药卵巢癌患者中比较度伐利尤单抗、奥拉帕利和西地尼布单药治疗、联合治疗或化疗：II期NRG-GY023试验
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.
作者信息
Lee Jung-Min, Miller Austin, Rose Peter G, AlHilli Mariam, Washington Christina, John Veena S, Shah Chirag A, Matsuo Koji, Siedel Jean, Miller David S, Hopp Elizabeth E, O'Shea Andrea, Chan John K, Bradford Leslie S, Morse Christopher B, Nagel Christa I, Rodabaugh Kerry J, Kohn Elise C, Moore Kathleen N, Liu Joyce F
机构信息
Women's Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
NRG Oncology, Clinical Trial Development Division, Department Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York.
出版信息
Clin Cancer Res. 2025 Jun 13;31(12):2370-2378. doi: 10.1158/1078-0432.CCR-24-3877.
PURPOSE
We assessed the efficacy of anti-PD-L1 durvalumab in combination with olaparib and cediranib (DOC), compared with the standard-of-care chemotherapy (SOC) in patients with platinum-resistant ovarian cancer (PROC), who had prior bevacizumab.
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. Patients were randomized 1:2:2:2 to SOC (weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin), DOC, durvalumab + cediranib (DC), or olaparib + cediranib (OC). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, overall response rate, and safety. 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. Experimental arms with HR estimates (vs. SOC) >0.87 could be discontinued.
RESULTS
A total of 153 patients were enrolled between April 4, 2021, and February 1, 2023. Accrual was permanently closed on February 1, 2023, due to futility. 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 survival was 7.5, 8.3, 5.7, and 10.2 months for SOC, DOC, DC, and OC, respectively. 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. 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. No new safety signals were observed.
CONCLUSIONS
In patients with PROC with prior bevacizumab, all experimental arms failed to reach the primary objective of improving PFS compared with SOC.
目的
我们评估了抗程序性死亡配体1（PD-L1）药物度伐利尤单抗联合奥拉帕利和西地尼布（DOC方案）与标准护理化疗（SOC）相比，在既往接受过贝伐单抗治疗的铂耐药卵巢癌（PROC）患者中的疗效。
患者与方法
NRG-GY023是第一项随机四臂优效性II期试验，纳入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PROC患者。患者按1:2:2:2随机分组至SOC组（每周紫杉醇、拓扑替康或聚乙二醇化脂质体阿霉素）、DOC组、度伐利尤单抗+西地尼布（DC组）或奥拉帕利+西地尼布（OC组）。主要终点是无进展生存期（PFS）。次要终点包括总生存期、总缓解率和安全性。该设计在每次与SOC进行比较时，采用单侧α = 0.1水平检验，检测风险比（HR）为0.5的效能为80%，并进行预先计划的中期分析。HR估计值（与SOC相比）>0.87的试验组可能会停止。
结果
2021年4月4日至2023年2月1日期间共纳入153例患者。由于无效，于2023年2月1日永久停止入组。截至2024年9月9日的数据截止时，SOC组、DOC组、DC组和OC组的中位PFS分别为3.4个月、2.9个月、2.5个月和2.8个月，中位总生存期分别为7.5个月、8.3个月、5.7个月和10.2个月。SOC组、DOC组、DC组和OC组的总缓解率分别为4.3%[95%置信区间（CI），0.00 - 0.19]、15.9%（95% CI，0.07 - 0.29）、11.9%（95% CI，0.05 - 0.24）和9.1%（95% CI，0.03 - 0.20）。与SOC组相比，DOC组、DC组和OC组的PFS HR估计值分别为1.003（95% CI，0.56 - 1.80）、1.108（95% CI，0.63 - 1.96）和1.021（95% CI，0.57 - 1.82）。未观察到新的安全信号。
结论
在既往接受过贝伐单抗治疗的PROC患者中，与SOC相比，所有试验组均未达到改善PFS的主要目标。
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