ATHENA–MONO (GOG-3020/ENGOT-ov45): A randomized, double-blind, phase 3 trial evaluating rucaparib monotherapy versus placebo as maintenance treatment following response to first-line platinum-based chemotherapy in ovarian cancer.

Bradley J. Monk GOG Foundation, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ info_outline Bradley J. Monk, Christine Parkinson, Myong Cheol Lim, David M. O'Malley, Ana Oaknin, Michelle K. Wilson, Robert L. Coleman, Domenica Lorusso, Amit M. Oza, Sharad A. Ghamande, Athina Christopoulou, Emily Prendergast, Fuat Demirkiran, Ramey D. Littell, Anita M. Chudecka-Glaz, Mark Aloysuis Morgan, Sandra M. Goble, Stephanie Hume, Keiichi Fujiwara, Rebecca Kristeleit

Authors Bradley J. Monk GOG Foundation, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ info_outline Bradley J. Monk, Christine Parkinson, Myong Cheol Lim, David M. O'Malley, Ana Oaknin, Michelle K. Wilson, Robert L. Coleman, Domenica Lorusso, Amit M. Oza, Sharad A. Ghamande, Athina Christopoulou, Emily Prendergast, Fuat Demirkiran, Ramey D. Littell, Anita M. Chudecka-Glaz, Mark Aloysuis Morgan, Sandra M. Goble, Stephanie Hume, Keiichi Fujiwara, Rebecca Kristeleit Organizations GOG Foundation, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ, Medical Oncology, Addenbrooke’s Hospital, Cambridge, United Kingdom, Gynecologic Oncology, National Cancer Center Korea, Goyang-Si, Gyeonggi-Do, South Korea, Division of Gynecologic Oncology, The Ohio State University, James Cancer Center, Columbus, OH, Gynaecologic Cancer Programme, Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain, Department of Cancer and Blood, Auckland City Hospital, Auckland, New Zealand, U.S. Oncology Research, The Woodlands, TX, MITO and Gynecologic Oncology Unit, Fondazione Universitario A. Policlinico Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy, Division of Medical Oncology and Hematology, Princess Margaret Hospital Cancer Centre, Toronto, ON, Canada, Department of Obstetrics and Gynecology, Augusta University, Augusta, GA, Medical Oncology Unit, St Andrews General Hospital of Patras, Patras, Greece, Gynecologic Oncology, Minnesota Oncology, Minneapolis, MN, Gynecologic Oncology Department, Medical Faculty, Istanbul University, Cerrahpaşa, Istanbul, Turkey, Kaiser Permanente Northern California Gynecologic Cancer Program, San Francisco, CA, Department of Surgical Gynecology and Gynecologic Oncology for Adults and Girls, Independent Public Clinical Hospital No. 2 PUM, Szczecin, Poland, Division Of Gynecologic Oncology, University of Pennsylvania Health System, Philadelphia, PA, Biostatistics, Clovis Oncology, Inc., Boulder, CO, Clinical Development, Clovis Oncology, Inc., Boulder, CO, Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Hidaka, Saitama, Japan, Department of Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: While PARP inhibitors have shown efficacy as first-line (1L) maintenance treatment for patients (pts) with ovarian cancer (OC), questions remain about the pt population that may benefit from their use. ATHENA (NCT03522246) was designed to test if rucaparib may be effective as 1L maintenance treatment in a broad pt population, including those without BRCA mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. Here we report results from the ATHENA–MONO comparison of rucaparib vs placebo. Methods: Pts with stage III–IV high-grade OC who had completed cytoreductive surgery (R0 permitted) and 4–8 cycles of 1L platinum-doublet (bevacizumab allowed with chemotherapy) with a response were randomized 4:1 to oral rucaparib 600 mg BID or placebo. Pts were stratified by HRD status (as determined by FoundationOne CDx), residual disease status after chemotherapy, and timing of surgery. The primary endpoint of investigator-assessed PFS per RECIST was assessed in a step-down procedure first in the HRD population (BRCA mutant or BRCA wild-type/loss of heterozygosity [LOH] high carcinoma) and then in the intent-to-treat (ITT) population. Blinded independent central review (BICR)–assessed PFS was a stand-alone, secondary endpoint. PFS in BRCA mutant and HRD-negative pts (BRCA wild-type/LOH low) were exploratory endpoints. Results: As of Mar 23, 2022 (visit cutoff), 427 and 111 pts were randomized to rucaparib monotherapy or placebo (median time on treatment, 14.7 and 9.9 mo). PFS data are shown in the Table. Most common grade ≥3 TEAEs were anemia (rucaparib, 28.7% vs placebo, 0%), neutropenia (14.6% vs 0.9%), and ALT/AST increased (10.6% vs 0.9%). Rucaparib dose reduction, interruption, and discontinuation due to TEAEs occurred in 49.4%, 60.7%, and 11.8% of pts. Conclusions: Rucaparib monotherapy is effective as 1L maintenance with significant benefit vs placebo observed in the ITT and HRD populations, as well as the non-nested subgroup of pts without known HRD. Clinical trial information: NCT03522246. Rucaparib, n (%) Placebo, n (%) Median investigator-assessed PFS, mo; log-rank P value HR (95% CI); P value Median BICR-assessed PFS, mo; log-rank P value HR (95% CI); P value Primary analyses HRD 185 (43%) 49 (44%) 28.7 vs 11.3; P =.0004 0.47 (0.31–0.72); P =.0005 NR vs 9.9; P =.0004 0.44 (0.28–0.70); P =.0005 ITT 427 (100%) 111 (100%) 20.2 vs 9.2; P <.0001 0.52 (0.40–0.68); P <.0001 25.9 vs 9.1; P <.0001 0.47 (0.36–0.63); P <.0001 Exploratory analyses ( P values are nominal, not adjusted for multiplicity) BRCA mutant 91 (21%) 24 (22%) NR vs 14.7; P =.0041 0.40 (0.21–0.75); P =.0045 NR vs NR; P =.0566 0.48 (0.23–1.00); P =.0512 HRD-negative 189 (44%) 49 (44%) 12.1 vs 9.1; P =.0284 0.65 (0.45–0.95); P =.0260 12.0 vs 6.4; P =.0119 0.60 (0.40–0.89); P =.0113