Gadducci Angiolo, Cosio Stefania
Department of Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, 56127 Pisa, Italy.
Cancers (Basel). 2021 Dec 7;13(24):6155. doi: 10.3390/cancers13246155.
Patients with metastatic or recurrent endometrial cancer (EC) not suitable for surgery and/or radiotherapy are candidates for pharmacological treatment frequently with unsatisfactory clinical outcomes. The purpose of this paper was to review the results obtained with chemotherapy, hormonal therapy, biological agents and immune checkpoint inhibitors in this clinical setting. The combination of carboplatin (CBDCA) + paclitaxel (PTX) is the standard first-line chemotherapy capable of achieving objective response rates (ORRs) of 43-62%, a median progression-free survival (PFS) of 5.3-15 months and a median overall survival (OS) of 13.2-37.0 months, respectively, whereas hormonal therapy is sometimes used in selected patients with slow-growing steroid receptor-positive EC. The combination of endocrine therapy with m-TOR inhibitors or cyclin-dependent kinase 4/6 inhibitors is currently under evaluation. Disappointing ORRs have been associated with epidermal growth factor receptor (EGFR) inhibitors, HER-2 inhibitors and multi-tyrosine kinase inhibitors used as single agents, and clinical trials evaluating the addition of bevacizumab to CBDCA + PTX have reported conflicting results. Immune checkpoint inhibitors, and especially pembrolizumab and dostarlimab, have achieved an objective response in 27-47% of highly pretreated patients with microsatellite instability-high (MSI-H)/mismatch repair (MMR)-deficient (-d) EC. In a recent study, the combination of lenvatinib + pembrolizumab produced a 24-week response rate of 38% in patients with highly pretreated EC, ranging from 64% in patients with MSI-H/MMR-d to 36% in those with microsatellite stable/MMR-proficient tumors. Four trials are currently investigating the addition of immune checkpoint inhibitors to PTX + CBDCA in primary advanced or recurrent EC, and two trials are comparing pembrolizumab + lenvatinib versus either CBDCA + PTX as a first-line treatment of advanced or recurrent EC or versus single-agent chemotherapy in advanced, recurrent or metastatic EC after one prior platinum-based chemotherapy.
对于无法进行手术和/或放疗的转移性或复发性子宫内膜癌（EC）患者，药物治疗是常用手段，但临床疗效往往不尽人意。本文旨在综述在这一临床背景下，化疗、激素治疗、生物制剂和免疫检查点抑制剂的治疗效果。卡铂（CBDCA）联合紫杉醇（PTX）是标准的一线化疗方案，客观缓解率（ORR）可达43%-62%，中位无进展生存期（PFS）为5.3-15个月，中位总生存期（OS）为13.2-37.0个月。激素治疗有时用于部分生长缓慢的类固醇受体阳性EC患者。内分泌治疗联合m-TOR抑制剂或细胞周期蛋白依赖性激酶4/6抑制剂目前正在评估中。表皮生长因子受体（EGFR）抑制剂、HER-2抑制剂和多酪氨酸激酶抑制剂单药使用时，ORR令人失望。评估贝伐单抗联合CBDCA+PTX的临床试验结果相互矛盾。免疫检查点抑制剂，尤其是帕博利珠单抗和多斯塔利单抗，在27%-47%的微卫星高度不稳定（MSI-H）/错配修复缺陷（MMR-d）的EC经治患者中取得了客观缓解。在一项近期研究中，乐伐替尼联合帕博利珠单抗在经治EC患者中的24周缓解率为38%，MSI-H/MMR-d患者为64%，微卫星稳定/MMR熟练肿瘤患者为36%。目前有四项试验正在研究在一线晚期或复发性EC中，免疫检查点抑制剂联合PTX+CBDCA的疗效。两项试验正在比较帕博利珠单抗联合乐伐替尼与CBDCA+PTX作为晚期或复发性EC的一线治疗方案，或与单药化疗用于一线铂类化疗后的晚期、复发性或转移性EC的疗效。
