Abstract：
Advanced recurrent endometrial cancer (EC) has a poor prognosis and new treatment options are needed. In 2013, EC was classified by genomic analysis into four groups: the POLE ultra-mutated group, the MSI-high hypermutated group (MSI-H), the copy number low group, and the copy number high group. The prognosis differs based on the classification, which should enable the individualization of treatment. The MSI-H and POLE types can induce PD-L1 expression in cancer cells. Among the gynecological cancers, EC exhibits the highest levels of PD-1 and PD-L1 expression and has the highest proportion of MSI-H. Thus, an immune checkpoint inhibitor (ICI) is expected to be effective. The first ICI to show efficacy in recurrent EC was the anti-PD1 antibody pembrolizumab, which exhibited efficacy in MSI-H EC. The combination of pembrolizumab and the multi-kinase inhibitor lenvatinib significantly prolongs OS/PFS compared with single-agent chemotherapy in previously treated recurrent EC, regardless of MSI status. ICIs are now moving from second-line and beyond to first-line treatment regimens. The efficacy of paclitaxel plus carboplatin (TC) and ICI combinations compared with TC have been demonstrated, including an ongoing Phase III trial comparing chemotherapy with the combination of pembrolizumab and lenvatinib. Although ICIs are becoming the mainstay of EC, they cause systemic inflammatory side effects known as irAEs. The incidence of irAEs is higher for combination therapy with CT or lenvatinib compared with ICI therapy alone. Even though they are rarely fatal, irAEs should be addressed promptly.
摘要：
晚期复发性子宫内膜癌（EC）预后不良，需要新的治疗选择。2013年，通过基因组分析将EC分为四组：POLE超突变组，MSI高超突变组（MSI-H），拷贝数低的组，和拷贝数高组。根据分类，预后有所不同，这应该能够实现治疗的个性化。MSI-H和POLE类型可以在癌细胞中诱导PD-L1表达。在妇科癌症中，EC表现出最高水平的PD-1和PD-L1表达，并且MSI-H的比例最高。因此，免疫检查点抑制剂（ICI）有望有效。在复发性EC中显示疗效的第一个ICI是抗PD1抗体pembrolizumab，在MSI-HEC中表现出疗效。pembrolizumab和多激酶抑制剂lenvatinib的组合与单一药物化疗相比，在先前治疗的复发性EC中显着延长OS/PFS。无论MSI状态如何。ICI现在正在从二线和二线治疗方案转向一线治疗方案。紫杉醇加卡铂（TC）和ICI组合与TC相比的疗效已得到证明，包括一项正在进行的III期试验，比较化疗与pembrolizumab和lenvatinib的组合。尽管ICI正在成为EC的支柱，它们会引起全身炎症副作用，称为irAE。与单独的ICI治疗相比，与CT或lenvatinib联合治疗的irAE发生率更高。即使它们很少致命，应迅速解决irAE。
