Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
University of Toronto, Toronto, ON, Canada.
Nat Commun. 2023 Mar 15;14(1):1452. doi: 10.1038/s41467-023-37084-w.
This multi-centre, non-randomized, open-label, phase II trial (NCT03016338), assessed niraparib monotherapy (cohort 1, C1), or niraparib and dostarlimab (cohort 2, C2) in patients with recurrent serous or endometrioid endometrial carcinoma. The primary endpoint was clinical benefit rate (CBR), with ≥5/22 overall considered of interest. Secondary outcomes were safety, objective response rate (ORR), duration of response, progression free survival and overall survival. Translational research was an exploratory outcome. Potential biomarkers were evaluated in archival tissue by immunohistochemistry and next generation sequencing panel. In C1, 25 patients were enrolled, and CBR was 20% (95% CI: 9-39) with median clinical benefit duration of 5.3 months. The ORR was 4% (95% CI: 0-20). In C2, 22 patients were enrolled, and the CBR was 31.8% (95% CI: 16-53) with median clinical benefit duration of 6.8 months. The ORR was 14% (95% CI: 3-35). No new safety signals were detected. No significant association was detected between clinical benefit and IHC markers (PTEN, p53, MMR, PD-L1), or molecular profiling (PTEN, TP53, homologous recombination repair genes). In conclusion, niraparib monotherapy did not meet the efficacy threshold. Niraparib in combination with dostarlimab showed modest activity.
这项多中心、非随机、开放标签、二期试验（NCT03016338）评估了尼拉帕利单药治疗（队列 1，C1）或尼拉帕利联合度伐利尤单抗（队列 2，C2）在复发性浆液性或子宫内膜样子宫内膜癌患者中的疗效。主要终点是临床获益率（CBR），≥5/22 例被认为有意义。次要终点是安全性、客观缓解率（ORR）、缓解持续时间、无进展生存期和总生存期。转化研究是一个探索性的结果。通过免疫组织化学和下一代测序面板对存档组织进行了潜在生物标志物的评估。在 C1 中，入组了 25 例患者，CBR 为 20%（95%CI：9-39），中位临床获益持续时间为 5.3 个月。ORR 为 4%（95%CI：0-20）。在 C2 中，入组了 22 例患者，CBR 为 31.8%（95%CI：16-53），中位临床获益持续时间为 6.8 个月。ORR 为 14%（95%CI：3-35）。未发现新的安全性信号。临床获益与 IHC 标志物（PTEN、p53、MMR、PD-L1）或分子谱分析（PTEN、TP53、同源重组修复基因）之间无显著相关性。总之，尼拉帕利单药治疗未达到疗效阈值。尼拉帕利联合度伐利尤单抗显示出一定的活性。
