Pembrolizumab plus chemotherapy in advanced or recurrent endometrial cancer: overall survival and exploratory analyses of the NRG GY018 phase 3 randomized trial

Mark S Shahin; Guilherme H Cantuaria; Eugenia Girda; Elizabeth Lokich; Juraj Kavecansky; Charles A Leath III; Lilian T Gien; Emily M Hinchcliff; Shashikant B Lele; Lisa M Landrum; Floor Backes; Roisin E O'Cearbhaill; Tareq Al Baghdadi; Ramez N Eskander; Emily K Hill; Michael W Sill; Premal H Thaker; Lindsey Beffa; Veena S John; Richard G Moore; Stephen Welch; Joanie M Hope; Amanda N Fader; Matthew A Powell; Fernanda B Musa; Robert S Mannel

doi:10.1038/s41591-025-03566-1

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Pembrolizumab plus chemotherapy in advanced or recurrent endometrial cancer: overall survival and exploratory analyses of the NRG GY018 phase 3 randomized trial

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Pembrolizumab plus chemotherapy in advanced or recurrent endometrial cancer: overall survival and exploratory analyses of the NRG GY018 phase 3 randomized trial

Mark S Shahin, Guilherme H Cantuaria, Eugenia Girda, Elizabeth Lokich, Juraj Kavecansky, Charles A Leath III, Lilian T Gien, Emily M Hinchcliff, Shashikant B Lele, Lisa M Landrum, …

Nature medicine, Vol.31(5), pp.1539-1546

05/2025

DOI: 10.1038/s41591-025-03566-1

PMCID: PMC12851417

PMID: 40044930

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Abstract

Historically, the treatment of patients with advanced stage or recurrent endometrial cancer included paclitaxel plus carboplatin. Immunotherapy in combination with chemotherapy resulted in improved clinical outcomes in several solid tumors. In the phase 3 NRG GY018 study, pembrolizumab plus chemotherapy significantly improved investigator-assessed progression-free survival (PFS; primary endpoint) versus placebo plus chemotherapy in patients with advanced/metastatic/recurrent endometrial cancer regardless of mismatch repair status. Here we report on key secondary endpoints and exploratory analyses. Patients were women ≥18 years old with newly diagnosed stage III or IVA endometrial cancer with measurable disease, or stage IVB or recurrent endometrial cancer with or without measurable disease. Patients (n = 810) were randomized (1:1) to pembrolizumab or placebo plus paclitaxel-carboplatin followed by maintenance pembrolizumab or placebo for up to 24 months. Overall survival was a secondary endpoint and PFS per RECIST v.1.1 by blinded independent central review was an exploratory endpoint. Overall survival data were immature; hazard ratios favored pembrolizumab (mismatch repair-proficient: 0.79 (0.53-1.17); 1-sided nominal P = 0.1157; mismatch repair-deficient: 0.55 (0.25-1.19); 1-sided nominal P = 0.0617). Hazard ratios (95% confidence intervals) for PFS per blinded independent central review favored pembrolizumab (mismatch repair-proficient: 0.64 (0.49-0.85); P = 0.0008; mismatch repair-deficient: 0.45 (0.27-0.73); P = 0.0005). These findings further support the use of pembrolizumab plus chemotherapy as first-line treatment for patients with advanced stage or recurrent endometrial cancer regardless of mismatch repair status. ClinicalTrials.gov identifier: NCT03914612 .

Details

Title: Subtitle: Pembrolizumab plus chemotherapy in advanced or recurrent endometrial cancer: overall survival and exploratory analyses of the NRG GY018 phase 3 randomized trial
Creators: Mark S Shahin - Thomas Jefferson University Hospital
Guilherme H Cantuaria - Georgia NCORP, Atlanta, GA, USA
Eugenia Girda - Rutgers, The State University of New Jersey
Elizabeth Lokich - Brown University
Juraj Kavecansky - Kaiser Permanente
Charles A Leath III - University of Alabama at Birmingham
Lilian T Gien - Sunnybrook Health Science Centre
Emily M Hinchcliff - Northwestern University
Shashikant B Lele - Roswell Park Comprehensive Cancer Center
Lisa M Landrum - Indiana University Health
Floor Backes - The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Roisin E O'Cearbhaill - Memorial Sloan Kettering Cancer Center
Tareq Al Baghdadi - Michigan Cancer Research Consortium
Ramez N Eskander - University of California San Diego
Emily K Hill - University of Iowa
Michael W Sill - Roswell Park Comprehensive Cancer Center
Premal H Thaker - Washington University in St. Louis
Lindsey Beffa - Cleveland Clinic
Veena S John - Northwell Health
Richard G Moore - University of Rochester Medical Center
Stephen Welch - London Regional Cancer Program, London, Ontario, Canada
Joanie M Hope - Alaska Women's Cancer Care
Amanda N Fader - Johns Hopkins University
Matthew A Powell - Washington University in St. Louis
Fernanda B Musa - Swedish Medical Center
Robert S Mannel - University of Oklahoma Health Sciences Center
Resource Type: Journal article
Publication Details: Nature medicine, Vol.31(5), pp.1539-1546
DOI: 10.1038/s41591-025-03566-1
PMID: 40044930
PMCID: PMC12851417
NLM abbreviation: Nat Med
ISSN: 1546-170X
eISSN: 1546-170X
Publisher: NATURE PORTFOLIO
Grant note: P30CA008748 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U10CA180822 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U10CA180868 / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
Language: English
Electronic publication date: 03/05/2025
Date published: 05/2025
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9984798226602771

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