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  • 2022-LBA-325-ESGO Patients with newly diagnosed ovarian cancer treated with maintenance rucaparib: exploratory biomarker analysis from the phase 3 ATHENA-MONO study (GOG-3020/ENGOT-ov45; NCT03522246)

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Late breaking abstracts
2022-LBA-325-ESGO Patients with newly diagnosed ovarian cancer treated with maintenance rucaparib: exploratory biomarker analysis from the phase 3 ATHENA-MONO study (GOG-3020/ENGOT-ov45; NCT03522246)
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  1. Ana Oaknin1,
  2. Rebecca S Kristeleit2,
  3. Haider S Mahdi3,4,
  4. Myong Cheol Lim5,
  5. Rocco de Vivo6,
  6. Erin A Salinas7,
  7. Michelle K Wilson8,
  8. Michalis Liontos9,
  9. Alessandro D Santin10,
  10. Diane M Provencher11,
  11. Fuat Demirkiran12,
  12. Lyndsay J Willmott13,
  13. Anita M Chudecka-Głaz14,
  14. Thomas J Herzog15,
  15. Mario E Beiner16,
  16. Larry J Copeland17,
  17. Iain A McNeish18,
  18. Kevin K Lin19 and
  19. Bradley J Monk20
  1. 1Gynaecologic Cancer Programme, Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
  2. 2Department of Oncology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
  3. 3Department of Obstetrics and Gynecology, Cleveland Clinic, Cleveland, OH
  4. 4*current location: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh
  5. 5Gynecologic Oncology, National Cancer Center Korea, Goyang-si, Gyeonggi-do, Republic of Korea, Korea, Republic of
  6. 6Department of Oncology, San Bortolo General Hospital, Azienda ULSS8 Berica, Vicenza, Italy
  7. 7Department of Gynecologic Oncology, Northwest Cancer Specialists PC, Vancouver, WA
  8. 8Department of Cancer and Blood, Auckland City Hospital, Auckland, New Zealand
  9. 9Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Alexandra Hospital, Athens, Greece
  10. 10Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, CT
  11. 11Department of Obstetrics-Gynaecology, Centre hospitalier de l’Université de Montréal (CHUM), Institut du cancer de Montréal, Montréal, QC, Canada
  12. 12Gynecologic Oncology Department, Medical Faculty, Istanbul University, Cerrahpaşa, Istanbul, Turkey
  13. 13Arizona Center for Cancer Care, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ
  14. 14Department of Gynaecological Surgery and Gynecological Oncology for Adults and Adolescents, Pomeranian Medical University, Szczecin, Poland
  15. 15Department of Gynecologic Oncology, University of Cincinnati, University of Cincinnati Cancer Center, Cincinnati, OH
  16. 16Gynecology-Oncology Department, Meir Medical Center, Kfar-Saba, Israel
  17. 17Department of Gynecologic Oncology, James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH
  18. 18Department of Surgery and Cancer, Imperial College London, London, UK
  19. 19Molecular Diagnostics, Clovis Oncology, Inc., Boulder, CO
  20. 20GOG Foundation, HonorHealth Research Institute, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, AZ

Abstract

Introduction In ATHENA-MONO, first-line (1L) maintenance treatment with rucaparib improved progression-free survival (PFS) versus placebo in patients with ovarian cancer (OC), regardless of molecular characteristics (Monk et al. J Clin Oncol. 2022). This exploratory analysis evaluated the PFS benefit of 1L maintenance rucaparib in subgroups defined by genomic biomarkers of homologous recombination deficiency, including homologous recombination repair (HRR) gene mutations, zygosity, and germline/somatic status.

Methods Patients with high-grade OC who underwent cytoreductive surgery and completed 1L platinum-doublet chemotherapy with a partial or complete response were randomised 4:1 to oral rucaparib 600 mg BID or placebo. Mutations in BRCA1, BRCA2, and 28 other genes in the HRR pathway (Coleman et al. Lancet. 2018), and zygosity status, were identified via next-generation sequencing of tumor tissues (Foundation Medicine). BRCA germline/somatic status were determined by germline sequencing (Ambry Genetics). The primary endpoint was investigator-assessed PFS per RECIST.

Results Deleterious mutations in BRCA1 and BRCA2 were detected in 13.9% (75/538) and 7.4% (40/538) of patients, respectively. PFS was longer with rucaparib compared with placebo in both BRCA1 (HR=0.39; 95% CI=0.14–1.08) and BRCA2 (HR=0.46; 95% CI=0.13–1.69) subgroups. Rucaparib PFS benefit was observed regardless of BRCA mutation type: short variants (frameshift, nonsense, splice site, missense) or large structural events (homozygous deletions, large rearrangements). BRCA mutations were further classified by germline (12.6%; 68/538), somatic (6.1%; 33/538), or unknown (2.6%; 14/538). PFS was longer with rucaparib compared with placebo in germline (HR=0.33; 95% CI=0.10–1.12) and somatic (HR=0.65; 95% CI=0.18–2.39) BRCA subgroups. Deleterious mutations in non-BRCA HRR genes were detected in 11.2% (60/538) of patients, with a PFS benefit of rucaparib versus placebo (HR=0.59; 95% CI=0.24–1.43).

Conclusions Exploratory biomarker analyses confirmed benefit with 1L maintenance rucaparib in patients with advanced OC harbouring different types of deleterious mutations in BRCA and non-BRCA HRR genes.

https://doi.org/10.1136/ijgc-2022-ESGO.1018

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