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.

AGO and Department Obstetrics and Gynecology University Hospital Mannheim Mannheim Germany

Biostatistics Clovis Oncology Inc Boulder CO

Cancer Trials Ireland and Department of Medical Oncology Cork University Hospital Cork Ireland

Clinical Development Clovis Oncology Inc Boulder CO

Clinical Operations Clovis Oncology Inc Boulder CO

College of Life Science National Tsing Hua University Hsinchu Taiwan

Department of Cancer and Blood Auckland City Hospital Auckland New Zealand

Department of Gynecologic Oncology and Reproductive Medicine University of Texas MD Anderson Cancer Center Houston TX

Department of Gynecologic Oncology Saitama Medical University International Medical Center Hidaka Saitama Japan

Department of Gynecologic Oncology Willamette Valley Cancer Institute and Research Center Eugene OR

Department of Gynecological Surgery and Gynecological Oncology of Adults and Adolescents Pomeranian Medical University Szczecin Poland

Department of Medical Oncology Sfantul Nectarie Oncology Center Dolj Romania

Department of Obstetrics and Gynaecology Faculty Hospital Kralovske Vinohrady 3rd Medical Faculty Charles University Prague Czech Republic

Department of Obstetrics and Gynecology Augusta University Augusta GA

Department of Obstetrics and Gynecology Chang Gung Memorial Hospital Tao Yuan Taiwan

Department of Obstetrics and Gynecology University of Sherbrooke Sherbrooke Quebec Canada

Department of Oncology Guy's and St Thomas' NHS Foundation Trust London United Kingdom

Department of Oncology Linköping University Linköping Sweden

Department of Surgery and Cancer Imperial College London London United Kingdom

Division of Gynaecological Oncology Department of Obstetrics and Gynecology Leuven Cancer Institute University Hospitals Leuven Leuven Belgium

Division of Gynecologic Oncology Department of Obstetrics and Gynecology College of Medicine University of Kentucky Lexington KY

Division of Gynecologic Oncology The Ohio State University James Cancer Center Columbus OH

Division of Gynecologic Oncology University of Pennsylvania Health System Philadelphia PA

GOG Foundation HonorHealth Research Institute University of Arizona College of Medicine Creighton University School of Medicine Phoenix AZ

Gynaecologic Cancer Programme Vall d'Hebron Institute of Oncology Hospital Universitari Vall d'Hebron Vall d'Hebron Barcelona Hospital Campus Barcelona Spain

Gynecologic Cancers Program Massachusetts General Hospital Harvard Medical School Boston MA

Gynecologic Oncology Department Medical Faculty Istanbul University Cerrahpaşa Istanbul Turkey

Gynecologic Oncology Minnesota Oncology and Metro Minnesota Community Oncology Research Consortium Minneapolis MN

Gynecologic Oncology National Cancer Center Korea Goyang si Gyeonggi do South Korea

Kaiser Permanente Northern California Gynecologic Cancer Program San Francisco CA

Limited Liability Company MedPomosch Saint Petersburg Russia

Medical Oncology Addenbrooke's Hospital Cambridge United Kingdom

Medical Oncology St Andrews General Hospital Patras Greece

MITO and Gynecologic Oncology Unit Fondazione Policlinico Universitario A Gemelli IRCCS and Catholic University of Sacred Heart Rome Italy

Molecular Diagnostics Clovis Oncology Inc Boulder CO

Nordic Society of Gynaecological Oncology Copenhagen Denmark

Oncology Department Tel Aviv Medical Center and Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

Princess Margaret Consortium and Department of Obstetrics Gynaecology Centre Hospitalier de l'Université de Montréal Institut du Cancer de Montréal Montréal Canada

Stevenson Cancer Center at the University of Oklahoma Health Sciences Center University of Oklahoma Health Sciences Center Oklahoma City OK

US Oncology Research The Woodlands TX

Women's Cancer Care Associates Division of Gynecologic Oncology Albany Medical College Albany NY

J Clin Oncol. 2023 Feb 1;41(4):935-936. doi: 10.1200/JCO.22.01585. PubMed

Ann Transl Med. 2023 Mar 31;11(6):272. doi: 10.21037/atm-2022-81. PubMed

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ClinicalTrials.gov
NCT03522246