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).

Autor:	Monk BJ; GOG Foundation, HonorHealth Research Institute, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ., Parkinson C; Medical Oncology, Addenbrooke's Hospital, Cambridge, United Kingdom., Lim MC; Gynecologic Oncology, National Cancer Center Korea, Goyang-si, Gyeonggi-do, South Korea., O'Malley DM; Division of Gynecologic Oncology, The Ohio State University, James Cancer Center, Columbus, OH., Oaknin A; Gynaecologic Cancer Programme, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain., Wilson MK; Department of Cancer and Blood, Auckland City Hospital, Auckland, New Zealand., Coleman RL; US Oncology Research, The Woodlands, TX., Lorusso D; MITO and Gynecologic Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy., Bessette P; Department of Obstetrics and Gynecology, University of Sherbrooke, Sherbrooke, Quebec, Canada., Ghamande S; Department of Obstetrics and Gynecology, Augusta University, Augusta, GA., Christopoulou A; Medical Oncology, St Andrews General Hospital, Patras, Greece., Provencher D; Princess Margaret Consortium and Department of Obstetrics-Gynaecology, Centre Hospitalier de l'Université de Montréal (CHUM), Institut du Cancer de Montréal, Montréal, Canada., Prendergast E; Gynecologic Oncology, Minnesota Oncology and Metro-Minnesota Community Oncology Research Consortium, Minneapolis, MN., Demirkiran F; Gynecologic Oncology Department, Medical Faculty, Istanbul University, Cerrahpaşa, Istanbul, Turkey., Mikheeva O; Limited Liability Company MedPomosch, Saint Petersburg, Russia., Yeku O; Gynecologic Cancers Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA., Chudecka-Glaz A; Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland., Schenker M; Department of Medical Oncology, Sfantul Nectarie Oncology Center, Dolj, Romania., Littell RD; Kaiser Permanente Northern California Gynecologic Cancer Program, San Francisco, CA., Safra T; Oncology Department, Tel Aviv Medical Center, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel., Chou HH; Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital (Linkou), Tao-Yuan, Taiwan.; College of Life Science, National Tsing Hua University, Hsinchu, Taiwan., Morgan MA; Division of Gynecologic Oncology, University of Pennsylvania Health System, Philadelphia, PA., Drochýtek V; Department of Obstetrics and Gynaecology, Faculty Hospital Kralovske Vinohrady, 3rd Medical Faculty, Charles University, Prague, Czech Republic., Barlin JN; Women's Cancer Care Associates, Division of Gynecologic Oncology, Albany Medical College, Albany, NY., Van Gorp T; Division of Gynaecological Oncology, Department of Obstetrics and Gynecology, Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium., Ueland F; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, College of Medicine, University of Kentucky, Lexington, KY., Lindahl G; Nordic Society of Gynaecological Oncology, Copenhagen, Denmark.; Department of Oncology, Linköping University, Linköping, Sweden., Anderson C; Department of Gynecologic Oncology, Willamette Valley Cancer Institute and Research Center, Eugene, OR., Collins DC; Cancer Trials Ireland and Department of Medical Oncology, Cork University Hospital, Cork, Ireland., Moore K; Stevenson Cancer Center at the University of Oklahoma Health Sciences Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Marme F; AGO and Department Obstetrics and Gynecology, University Hospital Mannheim, Mannheim, Germany., Westin SN; Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX., McNeish IA; Department of Surgery and Cancer, Imperial College London, London, United Kingdom., Shih D; Clinical Operations, Clovis Oncology Inc, Boulder, CO., Lin KK; Molecular Diagnostics, Clovis Oncology Inc, Boulder, CO., Goble S; Biostatistics, Clovis Oncology Inc, Boulder, CO., Hume S; Clinical Development, Clovis Oncology Inc, Boulder, CO., Fujiwara K; Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan., Kristeleit RS; Department of Oncology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2022 Dec 01; Vol. 40 (34), pp. 3952-3964. Date of Electronic Publication: 2022 Jun 06.
DOI:	10.1200/JCO.22.01003
Abstrakt:	Purpose: 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. Methods: 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. Results: 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%). Conclusion: Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD.
Databáze:	MEDLINE
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