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625 Dostarlimab + chemotherapy for the treatment of primary advanced or recurrent endometrial cancer: analysis of progression-free survival and overall survival outcomes by molecular classification in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial
  1. Mansoor Raza Mirza1,
  2. Sudarshan Sharma2,
  3. Jørn Herrstedt3,
  4. Mark S Shahin4,
  5. David Cibula5,
  6. Evelyn Fleming6,
  7. Francesco Raspagliesi7,
  8. Joseph Buscema8,
  9. Lars C Hanker9,
  10. Robert L Coleman10,
  11. Ingrid Boere11,
  12. Kellie Schneider12,
  13. Lucy Gilbert13,
  14. Brian Slomovitz14,
  15. Michael G Teneriello15,
  16. Matthew A Powell16,
  17. Srimoyee Ghosh17,
  18. Shadi Stevens18,
  19. Kari Ring19 and
  20. Ashley Stuckey20
  1. 1Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, and Nordic Society of Gynaecologic Oncology-Clinical Trial Unit, Copenhagen, Denmark
  2. 2Department of Obstetrics/Gynecology, AMITA Adventist Hinsdale Hospital, Hinsdale, USA
  3. 3Department of Clinical Oncology, Zealand University Hospital Roskilde, Roskilde, Denmark
  4. 4Hanjani Institute for Gynecologic Oncology, Abington Hospital-Jefferson Health, Asplundh Cancer Pavilion, Sidney Kimmel Medical College of Thomas Jefferson University, Willow Grove, USA
  5. 5Department of Obstetrics and Gynecology, General University Hospital in Prague, First Faculty of Medicine, Charles University, Prague, Czech Republic
  6. 6Division of Gynecologic Oncology, Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, USA
  7. 7Gynecological Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori – Milano, Milan, Italy
  8. 8Department of Gynecologic Oncology, Arizona Oncology, Tucson, USA
  9. 9Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, and AGO Study Group, Wiesbaden, Germany
  10. 10Sarah Cannon Research Institute, Nashville, USA
  11. 11Department of Medical Oncology, Erasmus MC Cancer Centre, Rotterdam, The Netherlands
  12. 12Norvant Health Cancer Institute – Elizabeth, Charlotte, USA
  13. 13Division of Gynecologic Oncology, McGill University Health Centre, Montreal, Canada
  14. 14Department of Gynecologic Oncology, Mount Sinai Medical Center, and the Department of Obstetrics and Gynecology, Florida International University, Miami Beach, USA
  15. 15US Oncology Research, The Woodlands, USA
  16. 16National Cancer Institute sponsored NRG Oncology, Washington University School of Medicine, St Louis, USA
  17. 17GSK, Waltham, USA
  18. 18GSK, London, UK
  19. 19Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Virginia, Charlottesville, USA
  20. 20Women and Infants Hospital, Providence, USA


Introduction/Background In the phase 3 RUBY trial (NCT03981796) dostarlimab + carboplatin-paclitaxel (CP) significantly improved progression-free survival (PFS) vs CP alone in the mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H; hazard ratio [HR], 0.28) and overall populations (HR, 0.64) with a favourable overall survival (OS) trend (HR, 0.64). Four molecular endometrial cancer subgroups were identified for prognostic and potential predictive value. Readily available validated surrogate methods include POLε mutation (mut), dMMR, TP53 abnormal, and no specific molecular profile (NSMP). Here, we present exploratory efficacy outcomes by molecular classification.

Methodology Patients with primary advanced or recurrent endometrial cancer were randomised 1:1 to receive dostarlimab or placebo, plus CP, followed by dostarlimab or placebo monotherapy for up to 3 years. POLε and TP53 status were determined by DNAseq; MMR/MSI status was determined by testing used for study enrolment (immunohistochemistry, polymerase chain reaction, or next-generation sequencing). Order of classification was POLεmut → dMMR/MSI-H → TP53mut → NSMP. PFS and OS were assessed for each subgroup.

Results Of 494 patients enrolled and randomised, mutational data were available for 400 patients (81.0%), classified as 5 (1.3%) POLεmut, 91 (22.8%) dMMR/MSI-H, 88 (22.0%) TP53mut, and 216 (54.0%) NSMP. PFS and OS results favoured the dostarlimab + CP arm in the dMMR/MSI-H, TP53mut, and NSMP subgroups, with the largest benefit observed in the dMMR and TP53mut groups. No patients with POLεmut had progression in either arm as of data cut (table 1).

Safety was reported previously.

Abstract 625 Table 1

Conclusion Dostarlimab + CP is associated with improved PFS and OS in the dMMR/MSI-H, NSMP, and TP53 subgroups and adds prognostic value in primary advanced or recurrent endometrial cancer. Patients with POLεmut had the best prognosis, as expected. Further research may help to validate these exploratory findings.

Disclosures Disclosures: This study (NCT03981796) was sponsored by GSK (Waltham, MA, USA).

Third-party medical writing support: Writing and editorial support, funded and coordinated by GSK, was provided by Shannon Morgan-Pelosi, PhD, and Mary C. Wiggin, of Ashfield MedComms, an Inizio company.

COI: Dr Mirza reports consulting fees from AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zailab; speakers’ bureau fees from AstraZeneca and GSK; research funding (to institution) from Apexigen, AstraZeneca, Deciphera (trial chair), GSK, and Ultimovacs; and personal financial interest in Karyopharm (stocks/shares, member of board of directors).

Dr Shahin reports institutional grants from AstraZeneca, GSK, and Merck; honoraria from AstraZeneca, GSK, Merck, and Seagen; expert testimony fees from Robinson & Havens PSC, Lexington, KY; advisory board fees from Seagen; and board member for Unite for Her.

Dr Cibula reports participation on an advisory board from Akesobio, AstraZeneca, GSK, MSD, Novocure, Roche, Seagen, and Sotio.

Dr Raspagliesi reports institutional grants or contracts from AstraZeneca; honoraria from MSD and GSK; travel support from GSK; and advisory board fees from PharmaMar.

Dr Hanker reports consulting/advisory fees from Amgen, AstraZeneca, Clovis, Eisai, GSK, Intuitive Surgery, Janssen, MSD, Novartis, Pfizer, Pharma Mar, Roche and Tesaro.

Dr Coleman reports grants or contracts from AstraZeneca, Clovis, Genelux, Genmab, Merck, Immunogen, and Roche/Genentech; consulting fees from AbbVie, Agenus, Alkermes, AstraZeneca, Clovis, Deciphera, Genelux, Genmab, GSK, Immunogen, Novocure, Merck, OncoQuest, Onxerna, Regeneron, and Roche/Genentech; honoraria from AstraZeneca, Clovis, Merck, and Roche/Genentech; and participation on a data safety monitoring board or advisory board from Eisai/BMS and VBL Therapeutics.

Dr Boere reports institutional research grant from GSK, and institutional advisory board meeting fees from AstraZeneca and GSK.

Dr Gilbert reports institutional grants from Alkermes, AstraZeneca, Clovis, Esperas, IMV, ImmunoGen Inc, Karyopharm, Merck Sharp & Dohme, Mersana, Novocure GmbH, OncoQuest Pharmaceuticals, Pfizer, Roche, and Tesaro; consulting fees from Merck; honoraria from Alkermes, AstraZeneca, Eisai, Eisai-Merck, and GSK.

Dr Slomovitz reports advisory fees from AstraZeneca, Clovis, Genentech, GSK, GOG Foundation, Merck, Myriad, Jazz Pharma, Onconova, Nuvation Bio, EQRX, Regeneron, Eisai, and Incyte; and board of directors for GOG Foundation and HOW: Hearing Ovarian Cancer Whispers.

Dr Powell reports consulting fees from GSK, Tesaro, Merck, Eisai, SeaGen, Clovis Oncology, and AstraZeneca.

Dr Stuckey reports royalties as an UptoDate reviewer.

Dr Buscema, Dr Fleming, Dr Herrstedt, Dr Ring, Dr Schneider, Dr Sharma, and Dr Teneriello have nothing to declare.

Dr Ghosh and Dr Stevens are employees of GSK.

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