Memorial Sloan Kettering Cancer Center and Weill Cornell Medical Center, New York, NY.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA.
J Clin Oncol. 2020 Jun 1;38(16):1814-1823. doi: 10.1200/JCO.19.02059. Epub 2020 Apr 10.
Single-agent PD-1 blockade exhibits limited efficacy in epithelial ovarian cancer (EOC). We evaluated ipilimumab plus nivolumab compared with nivolumab alone in women with persistent or recurrent EOC.
Eligibility criteria included measurable disease, 1-3 prior regimens, and platinum-free interval (PFI) < 12 months. Participants were randomly allocated to intravenous nivolumab (every 2 weeks) or induction with nivolumab plus ipilimumab for 4 doses (every 3 weeks), followed by every-2-week maintenance nivolumab for a maximum of 42 doses. The primary null hypothesis was equal probability of objective response within 6 months of random allocation in each arm.
One hundred patients were allocated to receive either nivolumab (n = 49), or nivolumab plus ipilimumab (n = 51), with PFI of < 6 months in 62%. Six (12.2%) responses occurred within 6 months in the nivolumab group and 16 (31.4%) in the nivolumab plus ipilimumab group (odds ratio, 3.28; 85% CI, 1.54 to infinity; = .034). The median progression-free survival (PFS) was 2 and 3.9 months in the nivolumab and nivolumab plus ipilimumab groups, respectively, with a PFI-stratified hazard ratio of 0.53 (95% CI, 0.34 to 0.82); the respective hazard ratio for death was 0.79 (95% CI, 0.44 to 1.42). Grade ≥ 3 related adverse events occurred in 33% of patients in the nivolumab group and 49% in the combination group, with no treatment-related deaths. PD-L1 expression was not significantly associated with response in either treatment group.
Compared with nivolumab alone, the combination of nivolumab and ipilimumab in EOC resulted in superior response rate and longer, albeit limited, PFS, with toxicity of the combination regimen comparable to prior reports. Additional combination studies to enhance durability of the dual regimen are warranted.
单药 PD-1 阻断在卵巢上皮癌（EOC）中的疗效有限。我们评估了伊匹单抗联合纳武利尤单抗与纳武利尤单抗单药治疗持续性或复发性 EOC 患者的疗效。
入选标准包括可测量疾病、既往治疗方案 1-3 种且铂类药物无进展间期（PFI）<12 个月。患者随机分配至静脉注射纳武利尤单抗（每 2 周一次）或纳武利尤单抗联合伊匹单抗诱导治疗 4 剂（每 3 周一次），随后每 2 周维持纳武利尤单抗治疗，最多 42 剂。主要零假设是在每个治疗组中，随机分组后 6 个月内客观缓解的概率相同。
100 例患者分配至纳武利尤单抗组（n=49）或纳武利尤单抗联合伊匹单抗组（n=51），其中 62%的患者 PFI<6 个月。纳武利尤单抗组中有 6 例（12.2%）在 6 个月内出现缓解，纳武利尤单抗联合伊匹单抗组中有 16 例（31.4%）（比值比，3.28；95%CI，1.54 至无穷大；=0.034）。纳武利尤单抗组和纳武利尤单抗联合伊匹单抗组的中位无进展生存期（PFS）分别为 2 个月和 3.9 个月，PFI 分层的风险比为 0.53（95%CI，0.34 至 0.82）；相应的死亡风险比为 0.79（95%CI，0.44 至 1.42）。纳武利尤单抗组 33%的患者出现≥3 级相关不良事件，联合组为 49%，但无治疗相关死亡。PD-L1 表达在两个治疗组中均与缓解无关。
与纳武利尤单抗单药治疗相比，EOC 中纳武利尤单抗联合伊匹单抗治疗可提高缓解率，并延长 PFS，尽管有限，但毒性与既往报道相当。需要进一步的联合研究来增强双重方案的持久性。
