Kuznicki Michelle L, Bennett Carrie, Yao Meng, Joehlin-Price Amy, Rose Peter G, Mahdi Haider
Cleveland Clinic, Women's Health Institute, Cleveland, OH, USA.
Cleveland Clinic, Quantitative Health Sciences, Cleveland, OH, USA.
Gynecol Oncol Rep. 2020 Nov 6;34:100671. doi: 10.1016/j.gore.2020.100671. eCollection 2020 Nov.
Prognostic factors for immune checkpoint inhibitor (CPI) response in gynecologic cancer are limited. This retrospective study aimed to identify prognostic factors associated with improved overall response rate (ORR) and progression free survival (PFS) in gynecologic cancer patients receiving at least two cycles of CPI. PFS was compared by univariate cox regressions. Univariate and multivariable analyses were used for prognostic factors of PFS and ORR. 72 patients were identified (20 ovarian, 36 endometrial, 13 cervix, 1 vaginal, 2 others). Immune related adverse events (IRAE) occurred in 40.3% of patients (29/72). IRAE was associated with higher ORR (44.8% IRAE vs 20.9% no IRAE, OR 3.1, p = 0.024), improved PFS (12.9 m IRAE vs 4.7 m no IRAE, HR 0.43, p = 0.004) and improved OS (22.9 m IRAE vs 12.2 m no IRAE, HR 0.47, p = 0.021). Additionally, Clear cell histology had superior ORR compared to MSI stable endometrial and ovarian cancers (ORR 57.1% vs 11.8%, OR 10.0, p = 0.032). Responders more often had ARIDIA mutation, PI3K/PTEN alteration and less often had a P53 mutation. In a subset of six MSI-H, recurrent, chemo-naive endometrial cancer ORR was 83.3%. Overall, we found favorable outcomes after CPI for clear cell tumors and patients who developed IRAE. Additionally, first-line systemic therapy with CPI in recurrent MSI-H endometrial cancer had encouraging ORR with durable responses.
妇科癌症中免疫检查点抑制剂（CPI）反应的预后因素有限。这项回顾性研究旨在确定在接受至少两个周期CPI治疗的妇科癌症患者中，与总体缓解率（ORR）提高和无进展生存期（PFS）相关的预后因素。通过单变量cox回归比较PFS。单变量和多变量分析用于PFS和ORR的预后因素。共纳入72例患者（20例卵巢癌、36例子宫内膜癌、13例宫颈癌、1例阴道癌、2例其他癌症）。40.3%的患者（29/72）发生了免疫相关不良事件（IRAE）。IRAE与更高的ORR相关（IRAE组为44.8%，无IRAE组为20.9%，OR为3.1，p = 0.024），PFS改善（IRAE组为12.9个月，无IRAE组为4.7个月，HR为0.43，p = 0.004）以及总生存期（OS）改善（IRAE组为22.9个月，无IRAE组为12.2个月，HR为0.47，p = 0.021）。此外，与微卫星稳定（MSI稳定）的子宫内膜癌和卵巢癌相比，透明细胞组织学具有更高的ORR（ORR为57.1%对11.8%，OR为10.0，p = 0.032）。缓解者更常发生ARIDIA突变、PI3K/PTEN改变，而P53突变较少见。在6例微卫星高度不稳定（MSI-H）、复发性、未接受过化疗的子宫内膜癌亚组中，ORR为83.3%。总体而言，我们发现CPI治疗后透明细胞肿瘤和发生IRAE的患者预后良好。此外，复发性MSI-H子宫内膜癌一线应用CPI全身治疗具有令人鼓舞的ORR和持久反应。
