Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
National Clinical Research Center for Obstetric and Gynecologic Diseases, Beijing, China.
Int J Gynecol Cancer. 2024 Nov 4;34(11):1761-1767. doi: 10.1136/ijgc-2024-005386.
Non-platinum chemotherapy is used in platinum resistant/refractory ovarian cancer patients but offers limited efficacy, especially in those who develop platinum resistance after ≤2 lines of platinum based chemotherapy. This phase II study aimed to evaluate the efficacy and safety of oral niraparib plus etoposide in platinum resistant/refractory ovarian cancer.
Platinum resistant/refractory ovarian cancer patients after ≤2 lines of platinum based chemotherapy, histologically confirmed as non-mucinous epithelial ovarian cancer, regardless of biomarker status, were eligible. Patients received niraparib with a starting dose of 200 mg/100 mg alternate once a day, and oral etoposide of 50 mg once a day, on days 1-20 of 30 days per cycle for a maximum of 6-8 cycles, followed by niraparib until disease progression or intolerable toxicity. The primary endpoint was investigator assessed progression free survival.
29 patients were enrolled from 22 May 2020 to 3 February 2023; 26 patients were included in the efficacy analysis set as per protocol. Median progression free survival was 4.2 months (95% confidence interval (CI) 3.9 to 4.4). Overall response rate was 26.9% (95% CI 8.7 to 45.2). Disease control rate was 57.7% (95% CI 37.3 to 78.0). Overall response rate in patients with a BRCA mutation and homologous recombination deficiency was 50% and 41.7%, respectively. Median progression free survival in patients with primary platinum resistance was 4.5 months (95% CI 3.6 to 5.3). 29 patients were included in the safety analysis set, and 8 (28%) patients experienced treatment related adverse events of grade ≥3. There was no treatment related discontinuation.
Niraparib combined with etoposide showed evidence of antitumor activity in platinum resistant/refractory ovarian cancer after ≤2 lines of platinum based chemotherapy, particularly in patients with a BRCA mutation, homologous recombination deficiency, or primary platinum resistance. This once-a-day oral combination was a convenient option.
NCT04217798.
铂耐药/难治性卵巢癌患者使用非铂类化疗药物，但疗效有限，尤其是在那些接受 2 线以上铂类化疗后发生铂耐药的患者中。本Ⅱ期研究旨在评估口服尼拉帕利联合依托泊苷在铂耐药/难治性卵巢癌中的疗效和安全性。
铂耐药/难治性卵巢癌患者，接受过≤2 线铂类化疗，组织学证实为非黏液性上皮性卵巢癌，无论生物标志物状态如何，均符合入组条件。患者接受尼拉帕利起始剂量为 200mg/100mg 交替口服，每天一次，依托泊苷 50mg 口服，每天一次，第 1-20 天，每 30 天为 1 个周期，最多 6-8 个周期，随后给予尼拉帕利治疗，直至疾病进展或出现不可耐受的毒性。主要终点为研究者评估的无进展生存期。
2020 年 5 月 22 日至 2023 年 2 月 3 日期间共招募了 29 名患者；根据方案，26 名患者纳入疗效分析集。中位无进展生存期为 4.2 个月（95%置信区间 3.9-4.4）。总缓解率为 26.9%（95%置信区间 8.7-45.2）。疾病控制率为 57.7%（95%置信区间 37.3-78.0）。BRCA 突变和同源重组缺陷患者的总缓解率分别为 50%和 41.7%。铂类耐药的患者中位无进展生存期为 4.5 个月（95%置信区间 3.6-5.3）。29 名患者纳入安全性分析集，8 名（28%）患者发生≥3 级治疗相关不良事件。无治疗相关停药。
尼拉帕利联合依托泊苷在铂耐药/难治性卵巢癌患者中显示出抗肿瘤活性的证据，这些患者接受了≤2 线铂类化疗，特别是在 BRCA 突变、同源重组缺陷或铂类耐药的患者中。这种每天口服的联合用药是一种方便的选择。
NCT04217798。
