Ovarian cancer is the second deadliest gynecologic malignancy globally. 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. 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. 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. 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 Germany and Gynecologic Oncology Center Kiel Germany

Beatson West of Scotland Cancer Centre and School of Cancer Sciences University of Glasgow UK

Cedars Sinai Medical Center Los Angeles CA USA

Department of Gynaecology Obstetrics and Neonatology 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Department of Medical Oncology University Medical Center Groningen University of Groningen Groningen the Netherlands

Department of Obstetrics and Gynecology University of Virginia School of Medicine Charlottesville VA USA

Division of Gynecologic Oncology Université de Montréal Montreal Quebec Canada

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

GSK Collegeville PA USA

GSK London UK

Gynecologic Oncology Division Rabin Medical Center Petah Tikva Israel

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

Hôpital Hôtel Dieu and University of Paris Paris France

Hospital Universitario La Paz IdiPAZ and GEICO Madrid Spain

Istituto Nazionale Tumori IRCCS Fondazione G Pascale Naples Italy

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

Rigshospitalet Copenhagen University Hospital Department of Cancer Treatment Copenhagen Denmark

Stephenson Cancer Center and University of Oklahoma Health Sciences Center Oklahoma City OK USA

Universitair Ziekenhuis Leuven Leuven Belgium

Citace poskytuje Crossref.org