Abstract
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.
Key words endometrial cancer - chemotherapy - radiotherapy - pembrolizumab - dostarlimab
