Advanced / Recurrent Endometrial Carcinoma: Systemic Therapy

Advanced / Recurrent Endometrial Carcinoma: overview

This algorithm addresses systemic therapy for advanced or recurrent endometrial carcinoma, with mismatch repair status as the first branch point. For dMMR or MSI-high disease, first-line options are carboplatin and paclitaxel plus dostarlimab (RUBY) or carboplatin and paclitaxel plus pembrolizumab (NRG-GY018). For MMR-proficient disease, the chart also shows carboplatin and paclitaxel plus immunotherapy, citing RUBY and NRG-GY018. In the site's summaries, both trials improved PFS in dMMR and all-comer populations, with the most pronounced benefit in dMMR tumors.

In later lines, the chart branches again by biomarker. For pMMR disease, pembrolizumab plus lenvatinib is shown (KEYNOTE-775), which improved PFS and OS over chemotherapy in previously treated disease, including pMMR tumors. For dMMR disease, single-agent checkpoint inhibition is supported by GARNET, in which dostarlimab produced durable responses in heavily pretreated dMMR/MSI-H endometrial carcinoma. HER2-positive serous carcinoma is directed to trastuzumab-based therapy.

Trials behind this algorithm

RUBY Mirza MR et al, NEJM, 2023; PMID: 36972026
NRG-GY018 Eskander RN et al, NEJM, 2023; PMID: 36972022
KEYNOTE-775 Makker V et al, NEJM, 2022; PMID: 35045221
GARNET Oaknin A et al, J Immunother Cancer, 2022; PMID: 35064011

Background reading: Endometrial cancer board review notes.

Advanced / Recurrent Endometrial Carcinoma: the algorithm in words

Starting point: Advanced / recurrent endometrial carcinoma. Full background: Endometrial cancer notes.

1L: dMMR / MSI-high (first-line): Chemo+IO: Carbo/paclitaxel + dostarlimab (RUBY); Chemo+IO: Carbo/paclitaxel + pembrolizumab (NRG-GY018).
1L: MMR-proficient (first-line): Chemo+IO: Carbo/paclitaxel + immunotherapy (RUBY / NRG-GY018).
Later-line (second-line): pMMR: Pembrolizumab + lenvatinib (KEYNOTE-775); dMMR: Single-agent checkpoint (GARNET); HER2+ serous: Trastuzumab-based (HER2-directed).