Tinker Anna V, Dhani Neesha C, Ghatage Prafull, McLeod Deanna, Samouëlian Vanessa, Welch Stephen A, Altman Alon D
BC Cancer-Vancouver, University of British Columbia, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada.
Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
Ther Adv Med Oncol. 2023 Mar 18;15:17588359231157633. doi: 10.1177/17588359231157633. eCollection 2023.
Endometrial cancer is a common malignancy and recurrences can be fatal. Although platinum-pretreated endometrial tumors are commonly treated with anthracyclines and taxanes, there is no current standard of care. Both immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) have been extensively assessed in this setting, including tumors selected for DNA mismatch repair (MMR)/microsatellite instability (MSI) and programmed death-ligand 1 expression status. This review will provide evidence-based guidance on use of ICIs alone or in combination with TKIs in patients with pretreated advanced, persistent, or recurrent metastatic endometrial cancer.
Randomized phase II-III trials in unselected populations pretreated, recurrent, or metastatic endometrial cancer and phase I-II trials in biomarker selected populations were identified from PubMed as well as conference proceedings using the key search terms 'immune checkpoint inhibitors', 'endometrial cancer', and 'advanced'.
A total of nine eligible studies were identified assessing ICI monotherapy for biomarker-selected or ICI plus TKI combinations and a dual ICI regimen for biomarker-unselected patients with pretreated recurrent or metastatic endometrial cancer. In MMR/MSI-selected tumors, five phase I/II studies evaluated ICI monotherapy indicating benefit in these patients. Only the phase III KEYNOTE-775 trial reported a statistically significant overall survival improvement for the combination of pembrolizumab plus lenvatinib compared with docetaxel or paclitaxel regardless of MMR/MSI status.
Pembrolizumab plus lenvatinib is indicated for patients with unselected pretreated metastatic endometrial cancer and pembrolizumab monotherapy is a preferred option for patients with MMRd/MSI-H tumors.
子宫内膜癌是一种常见的恶性肿瘤，复发可能致命。尽管铂类预处理过的子宫内膜肿瘤通常用蒽环类药物和紫杉烷类药物治疗，但目前尚无标准治疗方案。免疫检查点抑制剂（ICI）和酪氨酸激酶抑制剂（TKI）在这种情况下都已得到广泛评估，包括根据DNA错配修复（MMR）/微卫星不稳定性（MSI）和程序性死亡配体1表达状态选择的肿瘤。本综述将为预处理的晚期、持续性或复发性转移性子宫内膜癌患者单独使用ICI或ICI与TKI联合使用提供循证指导。
使用关键词“免疫检查点抑制剂”、“子宫内膜癌”和“晚期”，从PubMed以及会议论文集中识别未选择人群中预处理、复发或转移性子宫内膜癌的随机II-III期试验，以及生物标志物选择人群中的I-II期试验。
共识别出9项符合条件的研究，评估了生物标志物选择的ICI单药治疗或ICI加TKI联合治疗，以及生物标志物未选择的预处理复发或转移性子宫内膜癌患者的双ICI方案。在MMR/MSI选择的肿瘤中，5项I/II期研究评估了ICI单药治疗，表明对这些患者有益。只有III期KEYNOTE-775试验报告，无论MMR/MSI状态如何，帕博利珠单抗加乐伐替尼联合治疗与多西他赛或紫杉醇相比，总体生存率有统计学意义的改善。
帕博利珠单抗加乐伐替尼适用于未选择的预处理转移性子宫内膜癌患者，帕博利珠单抗单药治疗是MMRd/MSI-H肿瘤患者的首选方案。
