Tempfer Clemens, Brucker Sara, Juhasz-Boess Ingolf, Mallmann Peter, Steiner Eric, Denschlag Dominik, Hillemanns Peter, Wallwiener Markus, Beckmann Matthias W
Universitätsfrauenklinik der Ruhr Universität Bochum, Herne, Germany.
Universitäts-Frauenklinik Tübingen, Tübingen, Germany.
Geburtshilfe Frauenheilkd. 2023 Sep 12;83(9):1095-1101. doi: 10.1055/a-2145-1545. eCollection 2023 Sep.
The publication of two large randomized studies - the ENGOT-EN-6-NSGO/GOG-3031/RUBY trial and the NRG-GY018 trial - which investigated combining chemotherapy with immunotherapy to treat patients with primary advanced or recurrent endometrial cancer (EC) has transformed the clinical study landscape in terms of first-line therapy for affected patients and has set a new standard of therapy. In the ENGOT-EN-6-NSGO/GOG-3031/RUBY trial, the addition of dostarlimab to standard chemotherapy with carboplatin and paclitaxel resulted in a significant and clinically relevant improvement of progression-free survival and overall survival in the overall population, a significant and clinically relevant improvement of progression-free survival and overall survival in the subgroup with dMMR/MSI-high tumors, and a significant and clinically relevant improvement of progression-free survival in the subgroup with pMMR/MSI-low tumors. In the NRG-GY018 trial, the addition of pembrolizumab to standard chemotherapy with carboplatin and paclitaxel resulted in a significant and clinically relevant improvement of progression-free survival in the group with dMMR tumors, and a significant and clinically relevant improvement of progression-free survival in the group with pMMR tumors. As expected, the effect in both trials was much more pronounced in the group of patients with dMMR/MSI-high tumors. According to the assessment of the Uterus Organ Commission of the AGO, all patients with dMMR/MSI-high tumors should receive chemoimmunotherapy and all patients with pMMR/MSI-low tumors who meet the inclusion criteria of the two trials discussed here may have chemoimmunotherapy. For dostarlimab this means: patients with EC recurrence who will not undergo surgery or radiotherapy, patients with stage IIIA, IIIB or IIIC1 disease and a measurable lesion postoperatively, patients with stage IIIA, IIIB or IIIC1 disease with histological findings of serous EC, clear-cell EC or carcinosarcoma with or without a measurable lesion postoperatively, and patients with stage IIIC2 or IV disease with or without a measurable lesion postoperatively. For pembrolizumab this means: patients with EC recurrence (except carcinosarcoma) who will not undergo surgery or radiotherapy, and patients with stage III or IVA disease (except carcinosarcoma) and a measurable lesion postoperatively or with stage IVB disease with or without a measurable lesion.
两项大型随机研究——ENGOT-EN-6-NSGO/GOG-3031/RUBY试验和NRG-GY018试验——的发表，这两项试验研究了化疗联合免疫疗法治疗原发性晚期或复发性子宫内膜癌（EC）患者，在受影响患者的一线治疗方面改变了临床研究格局，并设定了新的治疗标准。在ENGOT-EN-6-NSGO/GOG-3031/RUBY试验中，在卡铂和紫杉醇标准化疗基础上加用多斯塔利单抗，使总体人群的无进展生存期和总生存期有显著且具有临床意义的改善，在错配修复缺陷（dMMR）/微卫星高度不稳定（MSI-H）肿瘤亚组中无进展生存期和总生存期有显著且具有临床意义的改善，在错配修复功能正常（pMMR）/微卫星低度不稳定（MSI-L）肿瘤亚组中无进展生存期有显著且具有临床意义的改善。在NRG-GY018试验中，在卡铂和紫杉醇标准化疗基础上加用帕博利珠单抗，使dMMR肿瘤组的无进展生存期有显著且具有临床意义的改善，在pMMR肿瘤组中无进展生存期也有显著且具有临床意义的改善。正如预期的那样，在dMMR/MSI-H肿瘤患者组中，两项试验的效果都更为显著。根据AGO子宫器官委员会的评估，所有dMMR/MSI-H肿瘤患者均应接受化疗免疫疗法，所有符合此处讨论的两项试验纳入标准的pMMR/MSI-L肿瘤患者也可接受化疗免疫疗法。对于多斯塔利单抗而言，这意味着：不会接受手术或放疗的EC复发患者、IIIA期、IIIB期或IIIC1期疾病且术后有可测量病灶的患者、IIIA期、IIIB期或IIIC1期疾病且组织学检查为浆液性EC、透明细胞EC或癌肉瘤且术后有或无可测量病灶的患者，以及IIIC2期或IV期疾病且术后有或无可测量病灶的患者。对于帕博利珠单抗而言，这意味着：不会接受手术或放疗的EC复发（癌肉瘤除外）患者，以及IIII期或IVA期疾病（癌肉瘤除外）且术后有可测量病灶或IVB期疾病且有或无可测量病灶的患者。
