Virginia Commonwealth University, Massey Cancer Center, Richmond, VA, USA.
The Ohio State University, James Comprehensive Cancer Center, Columbus, OH, USA.
Gynecol Oncol. 2023 Nov;178:161-169. doi: 10.1016/j.ygyno.2023.10.005. Epub 2023 Oct 25.
This study assessed the efficacy, safety, and health-related quality of life (HRQoL) of the treatment regimen of dostarlimab, a programmed death-1 inhibitor, combined with niraparib, a poly (ADP-ribose) polymerase inhibitor, in patients with BRCA wild type (BRCAwt) recurrent platinum-resistant ovarian cancer (PROC) who had previously received bevacizumab treatment.
This Phase II, open-label, single-arm, multicenter study, conducted in the USA, enrolled patients with recurrent PROC to receive niraparib and dostarlimab until disease progression or unacceptable toxicity (up to 3 years). A preplanned interim futility analysis was performed after the first 41 patients had undergone ≥1 radiographic evaluation (approximately 9 weeks from the first treatment).
The prespecified interim futility criterion was met and the study was therefore terminated. For the 41 patients assessed, the objective response rate (ORR) was 7.3% (95% confidence interval: 1.5-19.9); no patients achieved a complete response, 3 patients (7.3%) achieved a partial response (duration of response; 3.0, 3.8, and 9.2 months, respectively), and 9 patients (22.0%) had stable disease. In total, 39 patients (95.1%) experienced a treatment-related adverse event, but no new safety issues were observed. HRQoL, assessed using FOSI, or Functional Assessment of Cancer Therapy - Ovarian Symptom Index scores, worsened over time compared with baseline scores.
The study was terminated due to the observed ORR at the interim futility analysis. This highlights a need for effective therapies in treating patients with recurrent BRCAwt PROC.
本研究评估了程序性死亡-1 抑制剂 dostarlimab 联合聚（ADP-核糖）聚合酶抑制剂尼拉帕利在接受贝伐珠单抗治疗后复发的 BRCA 野生型（BRCAwt）铂耐药卵巢癌（PROC）患者中的疗效、安全性和健康相关生活质量（HRQoL）。
这项在美国进行的 II 期、开放标签、单臂、多中心研究招募了复发 PROC 的患者，接受尼拉帕利和 dostarlimab 治疗，直至疾病进展或不可接受的毒性（最长 3 年）。在首次接受≥1 次影像学评估（首次治疗后约 9 周）的 41 例患者中进行了预先计划的中期无效性分析。
达到了预定的中期无效性标准，因此研究终止。在评估的 41 例患者中，客观缓解率（ORR）为 7.3%（95%置信区间：1.5-19.9）；无完全缓解，3 例患者（7.3%）部分缓解（缓解持续时间分别为 3.0、3.8 和 9.2 个月），9 例患者（22.0%）病情稳定。共有 39 例患者（95.1%）发生了与治疗相关的不良事件，但未观察到新的安全性问题。使用 FOSI 或功能性评估癌症治疗卵巢症状指数评分评估 HRQoL ，与基线评分相比，随时间恶化。
由于中期无效性分析时观察到的 ORR，研究提前终止。这凸显了在治疗复发的 BRCAwt PROC 患者时需要有效的治疗方法。
