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Effect of progression-free interval (PFI) following penultimate platinum-based regimen on the efficacy of rucaparib maintenance treatment in patients with platinum-sensitive, recurrent ovarian carcinoma: an analysis from the phase 3 study ARIEL3
  1. AR Clamp1,
  2. AM Oza2,
  3. D Lorusso3,
  4. C Aghajanian4,
  5. A Oaknin5,
  6. A Dean6,
  7. N Colombo7,
  8. JI Weberpals8,
  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. T Cameron20,
  21. L Maloney21,
  22. S Goble22,
  23. RL Coleman23 and
  24. JA Ledermann24
  1. 1Department of Medical Oncology, The Christie NHS Foundation Trust and University of Manchester, Manchester, UK
  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. 7Gynecologic Cancer Program, European Institute of Oncology and University of Milan-Bicocca, Milan, Italy
  8. 8Division of Gynecologic Oncology, Ottawa Hospital Research Institute, Ottawa, ON, Canada
  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. 20Clinical Science, Clovis Oncology UK Ltd., Cambridge, UK
  21. 21Clinical Development
  22. 22Biostatistics, Clovis Oncology, Inc., Boulder, CO
  23. 23Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  24. 24Department of Oncology, UCL Cancer Institute, University College London and UCL Hospitals, London, UK


Introduction/Background In ARIEL3, rucaparib maintenance treatment significantly improved progression-free survival (PFS) vs placebo in all patient populations, regardless of biomarker status (Coleman et al. Lancet. 2017;390:1949–61). This subgroup analysis examined the effect of the stratification factor PFI following penultimate platinum-based chemotherapy (also a prognostic factor in ovarian cancer) on primary and secondary endpoints of investigator-assessed and blinded independent central review (BICR)-assessed PFS in ARIEL3.

Methodology Patients were randomised 2:1 to oral rucaparib (600 mg BID) or placebo. Analysis was based on the randomisation stratification factor of PFI following penultimate platinum-based regimen: 6–12 months or >12 months. PFS was assessed in 3 predefined cohorts: BRCA mutant; BRCA mutant + BRCA wild type/high loss of heterozygosity (LOH high); and intent-to-treat (ITT) population. Safety was assessed in all patients who received ≥1 dose of rucaparib.

Results Visit cutoff dates for efficacy and safety were 15 April 2017 and 31 December 2017, respectively. For all predefined cohorts, investigator and BICR assessments showed a significant PFS improvement with rucaparib vs placebo in both PFI subgroups (figure 1).

As expected, patients receiving placebo with a PFI 6–12 months had a shorter median PFS than those with a PFI >12 months. The treatment by PFI subgroup interaction was not significant, indicating that the treatment benefit was similar in both PFI subgroups. Safety data in the PFI subgroups were consistent with the overall study population, as previously reported.

Conclusion In ARIEL3, rucaparib maintenance treatment significantly improved PFS vs placebo in all cohorts, irrespective of PFI subgroup. The magnitude of treatment effect was similar for both PFI subgroups.

Disclosure ARC: AstraZeneca, Roche, Clovis 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 Pharmaceuticals, Specialised Therapeutics Australia NC: Clovis, Advaxis, AstraZeneca, BIOCAD, MSD, Pfizer, PharmaMar, Roche, Takeda, Tesaro JIW: AbbVie, AstraZeneca 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 BioPharma, 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 TC, LM, SG: Clovis RLC: Clovis, AbbVie, AstraZeneca, Esperance, Janssen, Merck, Millennium, OncoMed, Roche/Genentech, Bayer, GamaMabs, Genmab, Gradalis, Pfizer, Tesaro JAL: Clovis, AstraZeneca, Pfizer, Artios Pharma, Cristal Therapeutics, MSD, Regeneron, Roche, Seattle Genetics, Tesaro.

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