Statement of the Uterus Commission of the Gynecological Oncology Working Group (AGO) on the Use of Primary Chemoimmunotherapy to Treat Patients with Locally Advanced or Recurrent Endometrial Cancer

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

1. a significant and clinically relevant improvement of progression-free survival and overall survival in the overall population,

2. a significant and clinically relevant improvement of progression-free survival and overall survival in the subgroup with dMMR/MSI-high tumors, and

3. 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

1. a significant and clinically relevant improvement of progression-free survival in the group with dMMR tumors, and

2. 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:

1. patients with EC recurrence who will not undergo surgery or radiotherapy,

2. patients with stage IIIA, IIIB or IIIC1 disease and a measurable lesion postoperatively,

3. 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

4. patients with stage IIIC2 or IV disease with or without a measurable lesion postoperatively.

For pembrolizumab this means:

1. patients with EC recurrence (except carcinosarcoma) who will not undergo surgery or radiotherapy, and

2. 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

Publication History

Received: 07 July 2023

Accepted: 30 July 2023

Article published online:
12 September 2023

• References/Literatur

• 1 Mirza MR, Chase DM, Slomovitz BM. et al. RUBY Investigators. Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. N Engl J Med 2023; 388: 2145-2158
• 2 Eskander RN, Sill MW, Beffa L. et al. Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. N Engl J Med 2023; 388: 2159-2170
• 3 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF). S3-Leitlinie Endometriumkarzinom, Langversion 2.0, 2022, AWMF-Registernummer: 032/034-OL. Accessed June 24, 2023 at: https://www.leitlinienprogramm-onkologie.de/leitlinien/endometriumkarzinom/
• 4 Barlin JN, Puri I, Bristow RE. Cytoreductive surgery for advanced or recurrent endometrial cancer: a meta-analysis. Gynecol Oncol 2010; 118: 14-18
• 5 Creutzberg CL, van Putten WL, Koper PC. et al. PORTEC Study Group. Survival after relapse in patients with endometrial cancer: results from a randomized trial. Gynecol Oncol 2003; 89: 201-209
• 6 Chapman CH, Maghsoudi K, Littell RD. et al. Salvage high-dose-rate brachytherapy and external beam radiotherapy for isolated vaginal recurrences of endometrial cancer with no prior adjuvant therapy. Brachytherapy 2017; 16: 1152-1158
• 7 Ng TY, Perrin LC, Nicklin JL. et al. Local recurrence in high-risk node-negative stage I endometrial carcinoma treated with postoperative vaginal vault brachytherapy. Gynecol Oncol 2000; 79: 490-494
• 8 Vale CL, Tierney J, Bull SJ. et al. Chemotherapy for advanced, recurrent or metastatic endometrial carcinoma. Cochrane Database Syst Rev 2012; (2012) CD003915
• 9 Miller DS, Filiaci VL, Mannel RS. et al. Carboplatin and Paclitaxel for Advanced Endometrial Cancer: Final Overall Survival and Adverse Event Analysis of a Phase III Trial (NRG Oncology/GOG0209). J Clin Oncol 2020; 38: 3841-3850
• 10 Berek JS, Matias-Guiu X, Creutzberg C. et al. Endometrial Cancer Staging Subcommittee, FIGO Womenʼs Cancer Committee. FIGO staging of endometrial cancer: 2023. Int J Gynaecol Obstet 2023; DOI: 10.1002/ijgo.14923.
• 11 Matei D, Filiaci V, Randall ME. et al. Adjuvant Chemotherapy plus Radiation for Locally Advanced Endometrial Cancer. N Engl J Med 2019; 380: 2317-2326
• 12 Randall ME, Filiaci VL, Muss H. et al. Gynecologic Oncology Group Study. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 2006; 24: 36-44
• 13 de Boer SM, Powell ME, Mileshkin L. et al. PORTEC study group. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol 2018; 19: 295-309
• 14 de Boer SM, Powell ME, Mileshkin L. et al. PORTEC Study Group. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial. Lancet Oncol 2019; 20: 1273-1285
• 15 León-Castillo A, de Boer SM, Powell ME. et al. TransPORTEC consortium. Molecular Classification of the PORTEC-3 Trial for High-Risk Endometrial Cancer: Impact on Prognosis and Benefit From Adjuvant Therapy. J Clin Oncol 2020; 38: 3388-3397