BACKGROUND: Ovarian cancer is the second deadliest gynecologic malignancy globally. The current standard of care first-line therapy for newly diagnosed advanced epithelial ovarian cancer is surgery and platinum-based chemotherapy (±bevacizumab), followed by maintenance therapy with a poly(ADP-ribose) polymerase (PARP) inhibitor, bevacizumab, or a combination of the two. Although anti-programmed cell death (PD) protein 1 and anti-PD ligand 1 antibodies (PD-[L]1 inhibitors) have shown benefit in several solid tumors, their effect in ovarian cancer remains uncertain. Several trials are evaluating PD-(L)1 inhibitors in combination with first-line platinum-based chemotherapy and PARP inhibitor maintenance treatment. Here, we review trial designs to understand key similarities and differences for future assessments of the results. MATERIALS AND METHODS: The clinical trials registry "ClinicalTrials.gov" was searched using keywords, including ovarian cancer and niraparib, olaparib, or rucaparib. Search results were then filtered for phase 3 and manually reviewed to identify trials evaluating combinations of PARP inhibitors and PD-(L)1 inhibitors in the first-line setting. RESULTS: Four trials, ENGOT-OV44/FIRST (NCT03602859), ENGOT-OV46/AGO-OVAR 23/GOG-3025/DUO-O (NCT03737643), ENGOT-OV43/GOG-3036/KEYLYNK-001 (NCT03740165), and ENGOT-OV45/GOG-3020/ATHENA (NCT03522246), were identified. Of these, FIRST, DUO-O, and KEYLYNK-001 are evaluating both first-line use in combination with chemotherapy and maintenance, whereas ATHENA focuses on maintenance after a response to chemotherapy; however, DUO-O and KEYLYNK-001 do not include a PARP inhibitor in the comparator arm, limiting the ability to compare the added benefit of immunotherapy over the current standard of care. CONCLUSIONS: Results of these trials will determine whether PARP inhibitor and PD-(L)1 inhibitor combination with or without bevacizumab can improve patient outcomes.

AGO Study Group Wiesbaden 65185 Germany

Beatson West of Scotland Cancer Centre and School of Cancer Sciences University of Glasgow Glasgow G12 0YN United Kingdom

Department of Cancer Treatment Rigshospitalet Copenhagen University Hospital Copenhagen 2100 Denmark

Department of Gynaecology Obstetrics and Neonatology 1st Faculty of Medicine Charles University Prague 116 36; and General University Hospital Prague Prague 128 08 Czech Republic

Department of Gynecologic Oncology Universitair Ziekenhuis Leuven Leuven 3000 Belgium

Department of Gynecological Oncology Gynecologic Oncology Center Kiel 24105 Germany

Department of Medical Oncology Hospital Universitario La Paz IdiPAZ and GEICO Madrid 28046 Spain

Department of Medical Oncology University Medical Center Groningen University of Groningen Groningen 9700 RB The Netherlands

Department of Obstetrics and Gynecology Stephenson Cancer Center University of Oklahoma Health Sciences Center Oklahoma City OK 73104 United States

Department of Obstetrics and Gynecology University of Virginia School of Medicine Charlottesville VA 22903 United States

Division of Gynecologic Oncology Department of Obstetrics and Gynecology Cedars Sinai Medical Center Los Angeles CA 90048 United States

Division of Gynecologic Oncology Université de Montréal Montreal Quebec H2X 3E4 Canada

Faculty of Medical and Health Sciences University of Siedlce Siedlce 08 110 Poland

Global Medical Affairs GSK Collegeville PA 19426 United States

Global Medical Affairs GSK London W4 2HD United Kingdom

Gynecologic Oncology Division Rabin Medical Center Petah Tikva 4941492 Israel

HeCOG and Oncology Unit Aretaieion University Hospital National and Kapodistrian University of Athens Athens 115 28 Greece

Medical Oncology Department Hôpital Hôtel Dieu University of Paris Paris 75004 France

Oncologie Médicale Centre CARIO HPCA and Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens Plérin Sur Mer Plérin 22190 France

Uro Gynecologic Oncology Unit Istituto Nazionale Tumori IRCCS Fondazione G Pascale Naples 80131 Italy

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