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Patient-centred outcomes in the phase 3 study ARIEL3 of rucaparib maintenance treatment in patients with platinum-sensitive, recurrent ovarian carcinoma: post hoc exploratory analyses by BRCA mutation status and patient age
  1. N Colombo1,
  2. AM Oza2,
  3. D Lorusso3,
  4. C Aghajanian4,
  5. A Oaknin5,
  6. A Dean6,
  7. JI Weberpals7,
  8. AR Clamp8,
  9. G Scambia3,
  10. A Leary9,
  11. RW Holloway10,
  12. M Amenedo Gancedo11,
  13. PC Fong12,
  14. JC Goh13,14,
  15. DM O’Malley15,
  16. DK Armstrong16,
  17. S Banerjee17,
  18. J García-Donas18,
  19. EM Swisher19,
  20. J Meunier20,
  21. T Cameron21,
  22. L Maloney22,
  23. S Goble23,
  24. J Bedel24,
  25. RL Coleman25 and
  26. JA Ledermann26
  1. 1Gynecologic Cancer Program, European Institute of Oncology and University of Milan-Bicocca, Milan, Italy
  2. 2Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada
  3. 3Gynecologic Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
  4. 4Gynecologic Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
  5. 5Medical Oncology Department, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
  6. 6Department of Oncology, St John of God Subiaco Hospital, Subiaco, WA, Australia
  7. 7Division of Gynecologic Oncology, Ottawa Hospital Research Institute, Ottawa, ON, Canada
  8. 8Department of Medical Oncology, The Christie NHS Foundation Trust and University of Manchester, Manchester, UK
  9. 9Gynecological Unit, Gustave Roussy Cancer Center, INSERM U 981, and Groupe d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens (GINECO), Villejuif, France
  10. 10Department of Gynecologic Oncology, Florida Hospital Cancer Institute, Orlando, FL, USA
  11. 11Medical Oncology Department, Oncology Center of Galicia, La Coruña, Spain
  12. 12Medical Oncology Department, Auckland City Hospital, Grafton, Auckland, New Zealand
  13. 13Department of Oncology, Cancer Care Services, Royal Brisbane and Women’s Hospital, Herston
  14. 14University of Queensland, St Lucia, QLD, Australia
  15. 15Clinical Research Gynecologic Oncology, The Ohio State University, James Cancer Center, Columbus, OH
  16. 16Department of Medical Oncology, Johns Hopkins University Medical Center, Baltimore, MD, USA
  17. 17Medical Oncology Service, HM Hospitales—Centro Integral Oncológico Hospital de Madrid Clara Campal, Madrid, Spain
  18. 18Gynaecology Unit, The Royal Marsden NHS Foundation Trust, London, UK
  19. 19Division of Gynecologic Oncology, University of Washington, Seattle, WA, USA
  20. 20Modus Outcomes, Lyon, France
  21. 21Clinical Science, Clovis Oncology UK Ltd., Cambridge, UK
  22. 22Clinical Development
  23. 23Biostatistics, Clovis Oncology, Inc., Boulder, CO, USA
  24. 24Pricing and Market Access – Europe, Clovis Oncology Switzerland GmbH, Zurich, Switzerland
  25. 25Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  26. 26Department of Oncology, UCL Cancer Institute, University College London and UCL Hospitals, London, UK


Introduction/Background Maintenance therapy for recurrent ovarian cancer is intended to extend progression-free survival (PFS) without compromising patient quality of life; therefore, the clinical benefits of prolonged PFS should be evaluated in the context of toxicities that may compromise patients‘ wellbeing. In ARIEL3 (CO-338-014; NCT01968213), rucaparib significantly improved PFS vs placebo in all predefined patient cohorts regardless of biomarker status (Coleman et al. Lancet. 2017;390:1949-61) or age (Ledermann et al. Presented at SGO 2019; abst 4). This post hoc exploratory analysis examined quality-adjusted PFS (QA-PFS) and quality-adjusted time without symptoms or toxicity (Q-TWiST) in patients from ARIEL3, including the subgroup of patients with a BRCA mutation and subgroups based on patient age.

Methodology Patients were randomised 2:1 to oral rucaparib (600 mg BID) or placebo. QA-PFS and Q-TWiST were analysed in patients with a BRCA mutation (germline, somatic, or origin unknown), the ITT population (ie, all randomised patients), and subgroups of the ITT population defined by patient age at baseline (<65, 65–74, or ≥75 years). Q-TWiST was performed using 2 sets of treatment-emergent adverse events (TEAEs): all grade ≥3 TEAEs and grade ≥2 TEAEs of nausea, vomiting, fatigue, and asthenia only.

Results The visit cutoff date for these analyses was 15 April 2017. QA-PFS, Q-TWiST considering grade ≥3 TEAEs, and Q-TWiST considering select grade ≥2 TEAEs were significantly longer with rucaparib than placebo in patients with a BRCA mutation and in the ITT population (table). Across all age subgroups, QA-PFS and Q-TWiST (both analyses) were significantly longer with rucaparib than placebo (table 1).

Conclusion In the ITT population, BRCA-mutant subgroup, and age subgroups analysed, the quality-adjusted analyses, which incorporated patient-centred perspectives, confirmed the benefit of rucaparib vs placebo.

Disclosure NC: Clovis, Advaxis, AstraZeneca, BIOCAD, MSD, Pfizer, PharmaMar, Roche, Takeda, Tesaro AMO: Clovis, Amgen, Immunovaccine, Verastem, AstraZeneca, WebRx DL: Clovis, AstraZeneca, ImmunoGen, Merck, PharmaMar, Roche, Takeda, Tesaro CA: Clovis, Mateon, Bayer, Cerulean, Tesaro, VentiRx AO: Clovis, AstraZeneca, ImmunoGen, Genmab/Seattle Genetics, PharmaMar, Roche, Tesaro AD: Precision Oncology Australia, Shire, Specialised Therapeutics Australia JIW: AbbVie, AstraZeneca ARC: AstraZeneca, Roche, Clovis GS: Clovis, AstraZeneca, PharmaMar, Roche, Tesaro AL: Clovis, Pfizer, PharmaMar, GamaMabs, Merus, AstraZeneca RWH: Clovis, AstraZeneca, Tesaro MAG: Clovis, AstraZeneca, PharmaMar, Roche PCF: Clovis, AstraZeneca JCG: AstraZeneca, BMS, Janssen, Ipsen, MSD, Astellas DMO’M: Clovis, AstraZeneca, Gynecologic Oncology Group, Janssen, Myriad, Tesaro, Amgen, ImmunoGen, AbbVie, Ambry, Health Analytics, Agenus, Ajinomoto, Array, BMS, ERGOMED Clinical Research, Exelixis, Genentech, GSK, INC Research, inVentiv Health Clinical, Ludwig Institute for Cancer Research, Novartis, PRA International, Regeneron, Serono, Stemcentrx, TRACON DKA: Morphotek, Clovis, Advaxis, AstraZeneca, Pfizer, Syndax, Tesaro SB: Clovis, AstraZeneca, ImmunoGen, GamaMabs, Merck Serono, PharmaMar, Roche, Seattle Genetics, Tesaro JG-D: AstraZeneca, Clovis, Genentech/Roche, Janssen EMS: nothing to disclose JM: Modus Outcomes TC, LM, SG, JB: Clovis RLC: Clovis, AbbVie, AstraZeneca, Esperance, Janssen, Merck, Millennium, OncoMed, Roche/Genentech, Bayer, GamaMabs, Genmab, Gradalis, Millennium, Pfizer, Tesaro JAL: Clovis, AstraZeneca, Pfizer, Artios Pharma, Cristal Therapeutics, Merck/MSD, Regeneron, Roche, Seattle Genetics, Tesaro.

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