Oral Selinexor as Maintenance Therapy After First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer
This is another possibility for maintenance therapy. It will require further study.
Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial
Author(s): Shannon N. Westin, MD, MPH1; Kathleen Moore, MD2; Hye Sook Chon, MD3; Jung-Yun Lee, MD4; Jessica Thomes Pepin, MD5; Michael Sundborg, MD6; Ayelet Shai, MD, PhD7; Joseph de la Garza, MD8; Shin Nishio, MD9; Michael A. Gold, MD10; Ke Wang, MD11; Kristi McIntyre, MD12; Todd D. Tillmanns, MD13; Stephanie V. Blank, MD14; Ji-Hong Liu, MD15; Michael McCollum, MD16; Fernando Contreras Mejia, MD17; Tadaaki Nishikawa, MD18; Kathryn Pennington, MD19; Zoltan Novak, MD, PhD20; Andreia Cristina De Melo, MD21; Jalid Sehouli, MD22; Dagmara Klasa-Mazurkiewicz, MD23; Christos Papadimitriou, MD24; Marta Gil-Martin, MD25; Birute Brasiuniene, MD, PhD26; Conor Donnelly, PhD27; Paula Michelle del Rosario, MD28; Xiaochun Liu, MD, PhD29; Els Van Nieuwenhuysen, MD30
Source: https://doi.org/10.1200/JCO.23.02132
Dr. Anjan Patel's Thoughts
Initial results from the DUO-E study in metastatic endometrial cancer. The preliminary report suggests that maintenance durvalumab and maintenance durvalumab + olaparib were superior to standard observation after systemic carbo/taxol. As the trial data matures, the question will be: is this in all patients or driven by those with dMMR or HDR mutations?
PURPOSE
Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)–deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease.
METHODS
This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control.
RESULTS
Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1–positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents.
CONCLUSION
Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer.
Author Affiliations
1University of Texas MD Anderson Cancer Center, Houston, TX; 2Stephenson Cancer Center at the University of Oklahoma Medical Center, Oklahoma, OK; 3H.Lee Moffitt Cancer Center, Tampa, FL; 4Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Minnesota Oncology, Minneapolis, MN; 6FirstHealth Moore Regional Hospital, Pinehurst, NC; 7RAMBAM Health Care Campus, Haifa, and Israeli Society of Gynecologic Oncology (ISGO), Israel; 8Texas Oncology-San Antonio Medical Center, San Antonio, TX; 9Department of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Fukuoka, Japan; 10Oklahoma Cancer Specialists and Research Institute, Tulsa, OK; 11Tianjin Medical University Cancer Institute & Hospital, Tianjin, China; 12Texas Health Presbyterian Hospital, Dallas, TX; 13West Cancer Center Research Institute & University of Tennessee Health Science Center, Memphis, TN; 14Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, and GOG Foundation (GOG-F), USA; 15Sun Yat-sen University Cancer Center, Guangzhou, China; 16Virginia Oncology Associates, Brock Cancer Center, Norfolk, VA, and GOG Foundation (GOG-F), USA; 17National Cancer Institute of Colombia, Bogotá, Colombia; 18Department of Medical Oncology, National Cancer Center Hospital, Tokyo, Japan; 19Fred Hutchinson Cancer Center, University of Washington Medical Center, Seattle, WA; 20National Institute of Oncology, Budapest, and Central and Eastern European Gynecologic Oncology Group (CEEGOG), Hungary; 21Clinical Research and Technological Development Division, Brazilian National Cancer Institute, Rio de Janeiro, Brazil; 22Charité—Department of Gynecology with Center of Oncological Surgery, Universitätsmedizin Berlin, Berlin, and North Eastern German Society of Gynecological Oncology (NOGGO), Germany; 23Department of Obstetrics and Gynecology, Gynecological Oncology and Gynecological Endocrinology, Medical University of Gdańsk, Gdańsk, and Polish Gynecologic Oncology Group (PGOG), Poland; 24Aretaieion University Hospital, National and Kapodistrian University of Athens, Athens, and Hellenic Cooperative Oncology Group (HeCOG), Greece; 25Medical Oncology Department, Catalan Institute of Oncology-Institut d’Investigació Biomédica de Bellvitge (IDIBELL), Hospital Duran i Reynals, L’Hospitalet-Barcelona, Barcelona, and Grupo Español de Investigación en Cáncer de Ovario (GEICO), Spain; 26Department of Medical Oncology, National Cancer Institute of Lithuania, Faculty of Medicine of Vilnius University, Vilnius, and Nordic Society of Gynaecological Oncology (NSGO), Lithuania; 27Oncology Biometrics, AstraZeneca, Cambridge, United Kingdom; 28Oncology R&D, Global Medicines Development, AstraZeneca, Cambridge, United Kingdom; 29Oncology R&D, Late-stage Development, AstraZeneca, Gaithersburg, MD; 30University Hospital Leuven, Leuven, and Luxembourg Gynaecological Oncology Group (BGOG), BelgiumRelated Articles
Molecular Classification Predicts Response to Radiotherapy in the Randomized PORTEC-1 and PORTEC-2 Trials for Early-Stage Endometrioid Endometrial Cancer
An interesting study where the authors performed a post hoc analysis of randomized trials using molecular classification of endometrial cancers. There was good evidence to omit RT for those with POLE mutations and def-MMR. There seems to be a higher degree of benefit in those with a p53 mutation.
Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer
Large phase III study of carbo/taxol+pembro x 6 followed by pembro alone x 14 cycles in metastatic endometrial cancer. There was a benefit in both pMMR and dMMR patients, although the magnitude was unsurprisingly higher in those with dMMR. OS results are still pending, and carcinosarcoma-type histology was excluded. This combination has been approved and is on NCCN as a cat-1 recommendation.
Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer
Chemo + IO may become the SOC for 1L treatment of met-endometrial adenoCa. For pembro + chemo, there was a 70% lower risk of disease progression in dMMR and a 46% lower risk in pMMR compared to placebo + chemo. For pMMR patients, the impact on 2L therapy responses will need to be considered carefully, as lenvantinib + pembro has been found to be superior to either agent alone after chemo.
Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer
Chemo + IO may become the SOC for 1L treatment of met-endometrial adenoCa. For dostarlimab + chemo, there was an OS at 24 months of 83 vs. 58% in the dMMR and 67% vs. 55% in the pMMR groups compared to placebo + chemo. The question remains if chemo + IO is superior to IO alone in dMMR patients.
