Efficacy and safety of an oral combination therapy of niraparib and etoposide in platinum resistant/refractory ovarian cancer: a single arm, prospective, phase II study

Author:

Zhou Huimei,Liu Qian,Zhang Depu,Li Qingshui,Cao Dongyan,Cheng Ninghai,Wan Xirun,Zhang Ying,Feng Fengzhi,Xiang Yang,Yang JiaxinORCID

Abstract

ObjectiveNon-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.MethodsPlatinum 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.Results29 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.ConclusionsNiraparib 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.Trial registration numberNCT04217798

Funder

sponsored by Zai Lab (Shanghai) Co., Ltd

Publisher

BMJ

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