A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA–MONO/GOG-3020/ENGOT-ov45)
ATHENA (ClinicalTrials.gov identifier: NCT03522246) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA–MONO comparison of rucaparib versus placebo.
Patients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population.
As of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P = .0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P < .0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade ≥ 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%).
Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD.
Author Affiliations1GOG Foundation, HonorHealth Research Institute, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ 2Medical Oncology, Addenbrooke’s Hospital, Cambridge, United Kingdom 3Gynecologic Oncology, National Cancer Center Korea, Goyang-si, Gyeonggi-do, South Korea 4Division of Gynecologic Oncology, The Ohio State University, James Cancer Center, Columbus, OH 5Gynaecologic Cancer Programme, Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain 6Department of Cancer and Blood, Auckland City Hospital, Auckland, New Zealand 7US Oncology Research, The Woodlands, TX 8MITO and Gynecologic Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy 9Department of Obstetrics and Gynecology, University of Sherbrooke, Sherbrooke, Quebec, Canada 10Department of Obstetrics and Gynecology, Augusta University, Augusta, GA 11Medical Oncology, St Andrews General Hospital, Patras, Greece 12Princess Margaret Consortium and Department of Obstetrics-Gynaecology, Centre Hospitalier de l’Université de Montréal (CHUM), Institut du Cancer de Montréal, Montréal, Canada 13Gynecologic Oncology, Minnesota Oncology and Metro-Minnesota Community Oncology Research Consortium, Minneapolis, MN 14Gynecologic Oncology Department, Medical Faculty, Istanbul University, Cerrahpaşa, Istanbul, Turkey 15Limited Liability Company MedPomosch, Saint Petersburg, Russia 16Gynecologic Cancers Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA 17Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland 18Department of Medical Oncology, Sfantul Nectarie Oncology Center, Dolj, Romania 19Kaiser Permanente Northern California Gynecologic Cancer Program, San Francisco, CA 20Oncology Department, Tel Aviv Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel 21Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital (Linkou), Tao-Yuan, Taiwan 22College of Life Science, National Tsing Hua University, Hsinchu, Taiwan 23Division of Gynecologic Oncology, University of Pennsylvania Health System, Philadelphia, PA 24Department of Obstetrics and Gynaecology, Faculty Hospital Kralovske Vinohrady, 3rd Medical Faculty, Charles University, Prague, Czech Republic 25Women’s Cancer Care Associates, Division of Gynecologic Oncology, Albany Medical College, Albany, NY 26Division of Gynaecological Oncology, Department of Obstetrics and Gynecology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium 27Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, College of Medicine, University of Kentucky, Lexington, KY 28Nordic Society of Gynaecological Oncology, Copenhagen, Denmark 29Department of Oncology, Linköping University, Linköping, Sweden 30Department of Gynecologic Oncology, Willamette Valley Cancer Institute and Research Center, Eugene, OR 31Cancer Trials Ireland and Department of Medical Oncology, Cork University Hospital, Cork, Ireland 32Stevenson Cancer Center at the University of Oklahoma Health Sciences Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK 33AGO and Department Obstetrics and Gynecology, University Hospital Mannheim, Mannheim, Germany 34Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 35Department of Surgery and Cancer, Imperial College London, London, United Kingdom 36Clinical Operations, Clovis Oncology Inc, Boulder, CO 37Molecular Diagnostics, Clovis Oncology Inc, Boulder, CO 38Biostatistics, Clovis Oncology Inc, Boulder, CO 39Clinical Development, Clovis Oncology Inc, Boulder, CO 40Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan 41Department of Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom
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