Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Department of Gynecology, Cancer Institute Hospital of JFCR, Tokyo, Japan.
J Clin Oncol. 2021 Nov 20;39(33):3671-3681. doi: 10.1200/JCO.21.00334. Epub 2021 Sep 2.
This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer.
Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety.
Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; .002). There was no statistical difference in overall response rate between groups (7.6% 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% 98.1%), with no additional or new safety risks.
Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer.
本 III 期、多中心、随机、开放标签研究旨在评估纳武利尤单抗对比化疗（吉西他滨[GEM]或聚乙二醇脂质体多柔比星[PLD]）在铂耐药卵巢癌患者中的疗效和安全性。
符合条件的患者为铂耐药上皮性卵巢癌患者，在诊断耐药后接受了≤1 种治疗方案，且东部肿瘤协作组体能状态评分为≤1。患者按 1:1 随机分配至纳武利尤单抗（240 mg，每 2 周一次[一个周期]）或化疗组（GEM 1000 mg/m2，30 分钟滴注[第 1、8 和 15 天各一次]，随后休息 1 周[一个周期]）或 PLD 50 mg/m2，每 4 周一次[一个周期]）。主要结局为总生存期（OS）。次要结局包括无进展生存期（PFS）、总缓解率、缓解持续时间和安全性。
2015 年 10 月至 2017 年 12 月期间，316 例患者被随机分配至纳武利尤单抗（n=157）或 GEM 或 PLD（n=159）组。纳武利尤单抗和 GEM 或 PLD 组的中位 OS 分别为 10.1（95%CI，8.3 至 14.1）和 12.1（95%CI，9.3 至 15.3）个月（风险比，1.0；95%CI，0.8 至 1.3； =.808）。纳武利尤单抗和 GEM 或 PLD 组的中位 PFS 分别为 2.0（95%CI，1.9 至 2.2）和 3.8（95%CI，3.6 至 4.2）个月（风险比，1.5；95%CI，1.2 至 1.9；.002）。两组总缓解率无统计学差异（7.6% 13.2%；优势比，0.6；95%CI，0.2 至 1.3； =.191）。纳武利尤单抗组的中位缓解持续时间长于 GEM 或 PLD 组（18.7 7.4 个月）。纳武利尤单抗组与 GEM 或 PLD 组相比，治疗相关不良事件发生率较低（61.5% 98.1%），且未出现新的安全性风险。
尽管纳武利尤单抗耐受性良好，但与 GEM 或 PLD 相比，并未改善铂耐药卵巢癌患者的 OS，且 PFS 更差。
