Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Wilmot Cancer Institute, Department of Obstetrics and Gynecology, University of Rochester, Rochester, New York.
Clin Cancer Res. 2022 Oct 3;28(19):4186-4193. doi: 10.1158/1078-0432.CCR-21-1733.
The efficacy, safety, and tolerability of cediranib plus olaparib (cedi/ola) were investigated in patients with nongermline-BRCA-mutated (non-gBRCAm) platinum-resistant recurrent ovarian cancer.
PARP inhibitor-naïve women aged ≥18 years with platinum-resistant non-gBRCAm ovarian cancer, ECOG performance status of 0-2, and ≥3 prior lines of therapy received cediranib 30 mg once daily plus olaparib 200 mg twice daily in this single-arm, multicenter, phase IIb trial. The primary endpoint was objective response rate (ORR) by independent central review (ICR) using RECIST 1.1. Progression-free survival (PFS), overall survival (OS), and safety and tolerability were also examined.
Sixty patients received cedi/ola, all of whom had confirmed non-gBRCAm status. Patients had received a median of four lines of chemotherapy; most (88.3%) had received prior bevacizumab. ORR by ICR was 15.3%, median PFS was 5.1 months, and median OS was 13.2 months. Forty-four (73.3%) patients reported a grade ≥3 adverse event (AE), with one patient experiencing a grade 5 AE (sepsis), considered unrelated to the study treatment. Dose interruptions, reductions, and discontinuations due to AEs occurred in 55.0%, 18.3%, and 18.3% of patients, respectively. Patients with high global loss of heterozygosity (gLOH) had ORR of 26.7% [4/15; 95% confidence interval (CI), 7.8-55.1], while ORR was 12.5% (4/32; 95% CI, 3.5-29.0) in the low gLOH group.
Clinical activity was shown for the cedi/ola combination in heavily pretreated, non-gBRCAm, platinum-resistant patients with ovarian cancer despite failing to meet the target ORR of 20%, highlighting a need for further biomarker studies.
研究在非种系 BRCA 突变（非 gBRCAm）铂耐药复发性卵巢癌患者中，西地尼布联合奥拉帕利（cedi/ola）的疗效、安全性和耐受性。
这项单臂、多中心、IIb 期试验纳入了年龄≥18 岁、ECOG 体能状态为 0-2 分、既往接受过≥3 线治疗的铂耐药非 gBRCAm 卵巢癌、对 PARP 抑制剂初治的女性患者。主要终点是独立中心评估（ICR）使用 RECIST 1.1 评估的客观缓解率（ORR）。无进展生存期（PFS）、总生存期（OS）以及安全性和耐受性也进行了评估。
60 例患者接受了 cedi/ola 治疗，所有患者均有明确的非 gBRCAm 状态。患者接受了中位数为 4 线化疗；大多数（88.3%）患者曾接受过贝伐珠单抗治疗。ICR 评估的 ORR 为 15.3%，中位 PFS 为 5.1 个月，中位 OS 为 13.2 个月。44（73.3%）例患者报告了≥3 级不良事件（AE），1 例患者发生了 5 级 AE（败血症），认为与研究治疗无关。因 AE 导致的剂量中断、减量和停药分别占 55.0%、18.3%和 18.3%。高总体杂合性丢失（gLOH）患者的 ORR 为 26.7%[4/15；95%置信区间（CI），7.8-55.1]，而低 gLOH 组的 ORR 为 12.5%（4/32；95%CI，3.5-29.0）。
尽管未能达到 20%的目标 ORR，但在铂耐药、非 gBRCAm、既往治疗过的卵巢癌患者中，cedi/ola 联合治疗显示出了临床活性，这突出表明需要进一步进行生物标志物研究。
