Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Int J Gynecol Cancer. 2022 Aug 1;32(8):1017-1024. doi: 10.1136/ijgc-2022-003430.
Although immune checkpoint blockade has demonstrated limited effectiveness against ovarian cancer, subset analyses from completed trials suggest possible superior efficacy in the clear cell carcinoma subtype.
To describe the outcomes of patients with ovarian clear cell carcinoma treated with immune checkpoint blockade.
This was a single-institution, retrospective case series of patients with ovarian clear cell carcinoma treated with a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor with or without concomitant cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibition between January 2016 and June 2021. Demographic variables, tumor microenvironment, molecular data, and clinical outcomes were examined. Time to treatment failure was defined as the number of days between start of treatment and next line of treatment or death.
A total of 16 eligible patients were analyzed. The median treatment duration was 56 days (range 14-574); median time to treatment failure was 99 days (range 27-1568). The reason for discontinuation was disease progression in 88% of cases. Four patients (25%) experienced durable clinical benefit (time to treatment failure ≥180 days). One patient was treated twice with combined immune checkpoint blockade and experienced a complete response each time. All 12 patients who underwent clinical tumor-normal molecular profiling had microsatellite-stable disease, and all but one had low tumor mutation burden. Multiplex immunofluorescence analysis available from pre-treatment biopsies of two patients with clinical benefit demonstrated abundant tumor-infiltrating lymphocytes expressing PD-1.
Our study suggests a potential role for immune checkpoint blockade in patients with clear cell carcinoma of the ovary. Identification of genetic and microenvironmental biomarkers predictive of response will be key to guide therapy.
尽管免疫检查点阻断在卵巢癌中的疗效有限，但已完成的试验的亚组分析表明，其在透明细胞癌亚型中可能具有更好的疗效。
描述接受免疫检查点阻断治疗的卵巢透明细胞癌患者的结局。
这是一项单中心、回顾性病例系列研究，纳入了 2016 年 1 月至 2021 年 6 月期间接受程序性细胞死亡蛋白 1（PD-1）或程序性死亡配体 1（PD-L1）抑制剂治疗且伴有或不伴有同时使用细胞毒性 T 淋巴细胞相关蛋白 4（CTLA-4）抑制剂治疗的卵巢透明细胞癌患者。分析了患者的人口统计学变量、肿瘤微环境、分子数据和临床结局。治疗失败时间定义为从开始治疗到下一线治疗或死亡的天数。
共分析了 16 例符合条件的患者。中位治疗持续时间为 56 天（范围 14-574 天）；中位治疗失败时间为 99 天（范围 27-1568 天）。88%的病例因疾病进展而停药。4 例（25%）患者获得持久的临床获益（治疗失败时间≥180 天）。1 例患者接受了两次联合免疫检查点阻断治疗，每次均获得完全缓解。所有 12 例接受临床肿瘤-正常分子谱分析的患者均患有微卫星稳定疾病，除 1 例外，其余患者的肿瘤突变负担均较低。两名具有临床获益的患者的预处理活检标本进行了多重免疫荧光分析，结果显示大量表达 PD-1 的肿瘤浸润淋巴细胞。
我们的研究表明免疫检查点阻断在卵巢透明细胞癌患者中可能具有潜在作用。识别预测反应的遗传和微环境生物标志物将是指导治疗的关键。
