奥拉帕利单药或联合 Cediranib 与化疗治疗铂耐药卵巢癌的随机 II 期临床试验结果。
Results of a randomised Phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer.
机构信息
University College London Cancer Institute, London, UK.
Newcastle Clinical Trials Unit, Newcastle University, UK and Oncology Clinical Trials Office (OCTO), Department of Oncology, University of Oxford, Oxford, UK.
出版信息
Br J Cancer. 2024 Apr;130(6):941-950. doi: 10.1038/s41416-023-02567-6. Epub 2024 Jan 20.
BACKGROUND
OCTOVA compared the efficacy of olaparib (O) versus weekly paclitaxel (wP) or olaparib + cediranib (O + C) in recurrent ovarian cancer (OC).
AIMS
The main aim of the OCTOVA trial was to determine the progression-free survival (PFS) of olaparib (O) versus the oral combination of olaparib plus cediranib (O + C) and weekly paclitaxel (wP) in recurrent ovarian cancer (OC).
METHODS
In total, 139 participants who had relapsed within 12 months of platinum therapy were randomised to O (300 mg twice daily), wP (80 mg/m d1,8,15, q28) or O + C (300 mg twice daily/20 mg daily, respectively). The primary endpoint was progression-free survival (PFS) of olaparib (O) versus olaparib plus cediranib (O + C) or weekly paclitaxel (wP). The sample size was calculated to observe a PFS hazard ratio (HR) 0.64 in favour of O + C compared to O (20% one-sided type I error, 80% power).
RESULTS
The majority had platinum-resistant disease (90%), 22% prior PARPi, 34% prior anti-angiogenic therapy, 30% germline BRCA1/2 mutations. The PFS was increased for O + C vs O (O + C 5.4 mo (2.3, 9.6): O 3.7 mo (1.8, 7.6) HR = 0.73; 60% CI: 0.59, 0.89; P = 0.1) and no different between wP and O (wP 3.9 m (1.9, 9.1); O 3.7 mo (1.8, 7.6) HR = 0.89, 60% CI: 0.72, 1.09; P = 0.69). The main treatment-related adverse events included manageable diarrhoea (4% Grade 3) and hypertension (4% Grade 3) in the O + C arm.
DISCUSSION
OCTOVA demonstrated the activity of O + C in women with recurrent disease, offering a potential non-chemotherapy option.
TRIAL REGISTRATION
ISRCTN14784018, registered on 19th January 2018 http://www.isrctn.com/ISRCTN14784018 .
背景
OCTOVA 比较了奥拉帕利（O）与每周紫杉醇（wP）或奥拉帕利加西地尼布（O+C）在复发性卵巢癌（OC）中的疗效。
目的
OCTOVA 试验的主要目的是确定奥拉帕利（O）与奥拉帕利加西地尼布（O+C）联合每周紫杉醇（wP）在复发性卵巢癌（OC）中的无进展生存期（PFS）。
方法
共有 139 名在铂类治疗后 12 个月内复发的患者被随机分为 O（300mg 每日 2 次）、wP（80mg/m2 d1、8、15、q28）或 O+C（300mg 每日 2 次/20mg 每日）。主要终点是奥拉帕利（O）与奥拉帕利加西地尼布（O+C）或每周紫杉醇（wP）的无进展生存期（PFS）。根据观察 O+C 对比 O 的 PFS 危险比（HR）为 0.64 的方案计算样本量（20%单侧Ⅰ类错误，80%效能）。
结果
大多数患者有铂类耐药性疾病（90%）、22%患者曾使用 PARPi、34%患者曾使用抗血管生成治疗、30%患者有胚系 BRCA1/2 突变。O+C 对比 O 的 PFS 增加（O+C 5.4 个月（2.3，9.6）：O 3.7 个月（1.8，7.6）HR=0.73；60%CI：0.59，0.89；P=0.1），而 wP 与 O 之间无差异（wP 3.9 个月（1.9，9.1）：O 3.7 个月（1.8，7.6）HR=0.89，60%CI：0.72，1.09；P=0.69）。主要的治疗相关不良事件包括 O+C 组可管理的腹泻（4%为 3 级）和高血压（4%为 3 级）。
讨论
OCTOVA 显示 O+C 在复发性疾病患者中具有活性，为非化疗选择提供了潜力。
试验注册
ISRCTN14784018，于 2018 年 1 月 19 日注册，http://www.isrctn.com/ISRCTN14784018。
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