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619 Durvalumab plus carboplatin/paclitaxel followed by durvalumab ± olaparib as a first-line treatment for newly diagnosed advanced or recurrent endometrial cancer: results from the phase III DUO-E/GOG-3041/ENGOT-EN10 Trial
  1. Shannon N Westin1,
  2. Kathleen N Moore2,
  3. Hye Sook Chon3,
  4. Jung-Yun Lee4,
  5. Jessica Thomes Pepin5,
  6. Michael Sundborg6,
  7. Joseph De La Garza7,
  8. Shin Nishio8,
  9. Ke Wang9,
  10. Kristi Mcintyre10,
  11. Todd D Tillmanns11,
  12. Fernando Contreras Mejia12,
  13. Andreia Cristina De Melo13,
  14. Dagmara Klasa-Mazurkewicz14,
  15. Christos Papadimitriou15,
  16. Marta Gil-Martin16,
  17. Birute Brasiuniene17,
  18. Conor Donnelly18,
  19. Xiaochun Liu19 and
  20. Els Van Nieuwenhuysen20
  1. 1University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  2. 2University of Oklahoma Medical Center, Oklahoma City, Oklahoma, USA
  3. 3Moffitt Cancer Center, University of South Florida, Tampa, Florida, USA
  4. 4Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, South Korea
  5. 5Minnesota Oncology, Maplewood, Minnesota, USA
  6. 6FirstHealth Moore Regional Hospital, Pinehurst, North Carolina, USA
  7. 7Texas Oncology-San Antonio Medical Center, San Antonio, Texas, USA
  8. 8Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Fukuoka, Japan
  9. 9Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
  10. 10Texas Health Presbyterian Hospital, Dallas, Texas, USA
  11. 11West Cancer Center, Germantown, Tennessee, USA
  12. 12National Cancer Institute of Colombia, Bogotá, Colombia
  13. 13Clinical Research and Technological Development Division, Brazilian National Cancer Institute, Rio De Janeiro, Brazil
  14. 14Department of Obstetrics and Gynecology, Gynecological Oncology and Gynecological Endocrinology, Medical University of Gdansk, and PGOG, Gdansk, Poland
  15. 152nd Department of Surgery, Aretaieion Hospital, The National and Kapodistrian University of Athens, and HeCOG, Athens, Greece
  16. 16Medical Oncology Department, Catalan Institute of Oncology-Institut d’Investigació Biomèdica de Bellvitge (IDIBELL), Hospital Duran i Reynals, L’Hospitalet-Barcelona, and GEICO, Barcelona, Spain
  17. 17Department of Medical Oncology, National Cancer Institute of Lithuania, Faculty of Medicine of Vilnius University, and NSGO, Vilnius, Lithuania
  18. 18Oncology Biometrics, AstraZeneca, Cambridge, UK
  19. 19Oncology RandD, Late-Stage Development, AstraZeneca, Gaithersburg, Maryland, USA
  20. 20UZ Leuven, and BGOG, Leuven, Belgium

Abstract

Introduction/Background Combination of immunotherapy with carboplatin/paclitaxel (CP) has demonstrated improved progression-free survival (PFS) and overall survival (OS) in patients with advanced endometrial cancer. The Phase III DUO-E/GOG-3041/ENGOT-EN10 trial (NCT04269200) evaluated the addition of durvalumab to standard first-line CP, followed by durvalumab ± olaparib, in patients with endometrial cancer.

Methodology Patients with newly diagnosed Federation of Gynecology and Obstetrics Stage III/IV or recurrent endometrial cancer and naïve to systemic treatment were randomised 1:1:1 to CP (CP+durvalumab placebo for six cycles followed by durvalumab placebo+olaparib placebo); CP+durvalumab (CP+durvalumab [1120 mg IV q3w] for six cycles followed by durvalumab [1500 mg IV q4w]+olaparib placebo); or CP+durvalumab+olaparib (CP+durvalumab for six cycles followed by durvalumab+olaparib [300 mg tablets bid]). Dual primary endpoints were PFS (investigator-assessed Response Evaluation Criteria in Solid Tumors v1.1) in the intent-to-treat (ITT) population for CP+durvalumab versus CP and CP+durvalumab+olaparib versus CP. OS was a secondary endpoint. A multiple-testing procedure with gatekeeping strategy was applied to PFS and OS. PFS by mismatch repair (MMR) status was a prespecified subgroup analysis.

Results In the ITT population (N=718), CP+durvalumab and CP+durvalumab+olaparib showed statistically significant and clinically meaningful PFS benefit versus CP (table 1). First interim OS data (27.7% mature) showed a trend towards benefit (CP+durvalumab versus CP: hazard ratio [95% confidence interval] 0.77 [0.56–1.07; P=0.120]; CP+durvalumab+olaparib versus CP: 0.59 [0.42–0.83; P=0.003]). PFS subgroup analysis showed benefit for both arms versus CP in MMR-deficient (dMMR; n=143) and MMR-proficient (pMMR; n=575) patients. In pMMR patients, maintenance olaparib further enhanced PFS benefit (table 1). Safety profiles of the treatment arms were generally consistent with individual components.

Abstract 619 Table 1

Conclusion DUO-E met both primary endpoints, showing statistically significant and clinically meaningful PFS improvement with the addition of durvalumab to CP followed by durvalumab ± olaparib versus CP alone. Maintenance olaparib further improved PFS in patients with pMMR disease.

Disclosures This study was funded by AstraZeneca.

Previously presented at ESMO 2023, FPN (Final Publication Number): LBA41, S. N. Westin et al – reused with permission.

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