Nicoletta Colombo1, Amit M Oza2, Domenica Lorusso3, Carol Aghajanian4, Ana Oaknin5, Andrew Dean6, Johanne I Weberpals7, Andrew R Clamp8, Giovanni Scambia3, Alexandra Leary9, Robert W Holloway10, Margarita Amenedo Gancedo11, Peter C Fong12, Jeffrey C Goh13, David M O'Malley14, Deborah K Armstrong15, Susana Banerjee16, Jesus García-Donas17, Elizabeth M Swisher18, Juliette Meunier19, Terri Cameron20, Lara Maloney21, Sandra Goble22, Josh Bedel23, Jonathan A Ledermann24, Robert L Coleman25. 1. Gynecologic Cancer Program, University of Milan-Bicocca and European Institute of Oncology IRCCS, via Ripamonti 435, 20146 Milan, Italy. Electronic address: nicoletta.colombo@ieo.it. 2. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, 610 University Ave, Toronto, ON, Canada. 3. Gynecologic Oncology Unit, Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy. 4. Gynecologic Medical Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA. 5. Medical Oncology Department, Vall d'Hebron Institute of Oncology, C/Natzaret, 115-117, 08035 Barcelona, Spain. 6. Department of Medical Oncology, St John of God Hospital Subiaco, 12 Salvado Rd, Subiaco, WA 6008, Australia. 7. Division of Gynecologic Oncology, Ottawa Hospital Research Institute, 501 Smyth Rd, Ottawa, ON K1H 8L6, Canada. 8. Department of Medical Oncology, The Christie NHS Foundation Trust and University of Manchester, Manchester M20 4BX, UK. 9. Gynecological Unit, Gustave Roussy Cancer Center, INSERM U981, and Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), 98405 Villejuif, France. 10. Gynecologic Oncology, Advent Health Cancer Institute, 601 East Rollins St, Orlando, FL 32803, USA. 11. Medical Oncology Department, Oncology Center of Galicia, Rúa Doctor Camilo Veiras, 1, 15009 La Coruña, Spain. 12. Medical Oncology Department, Auckland City Hospital, Grafton, 2 Park Road, Grafton, Auckland 1023, New Zealand. 13. Department of Oncology, Cancer Care Services, Royal Brisbane and Women's Hospital, and University of Queensland, Cnr Butterfield St and Bowen Bridge Rd, Herston, QLD 4029, Australia. 14. Gynecologic Oncology, James Cancer Center, The Ohio State University, Starling-Loving Hall, 320 West 10th Ave, Columbus, OH 43210, USA. 15. Gynecology and Obstetrics, Johns Hopkins University Medical Center, 601 N Caroline St, Baltimore, MD 21287, USA. 16. Gynaecology Unit, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, Fulham Road, London SW3 6JJ, UK. 17. Division of Medical Oncology, HM Hospitales-Centro Integral Oncológico Hospital de Madrid Clara Campal, Calle Oña 10, 28050 Sanchinarro, Madrid, Spain. 18. Division of Gynecologic Oncology, University of Washington, 1959 NE Pacific Street, Box 356460, Seattle, WA 98195, USA. 19. Modus Outcomes, 61 Cours de la Liberte, 69003 Lyon, France. 20. Clinical Science, Clovis Oncology UK Ltd., Granta Centre, Granta Park, Great Abington, Cambridge CB21 6GP, UK. 21. Clinical Development, Clovis Oncology, Inc., 5500 Flatiron Parkway, Boulder, CO 80301, USA. 22. Biostatistics, Clovis Oncology, Inc., 5500 Flatiron Parkway, Boulder, CO 80301, USA. 23. Pricing & Market Access - Europe, Clovis Oncology Switzerland GmBH, Seefeldstrasse 69, 8008 Zurich, Switzerland. 24. Department of Oncology, UCL Cancer Institute, University College London and UCL Hospitals, 72 Huntley St, London WC1E 6DD, UK. 25. Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
Abstract
BACKGROUND: In the phase 3 trial ARIEL3, maintenance treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib provided clinical benefit versus placebo for patients with recurrent, platinum-sensitive ovarian cancer. Here, we evaluate the impact of age on the clinical utility of rucaparib in ARIEL3. METHODS:Patients with platinum-sensitive, recurrent ovarian carcinoma with ≥2 prior platinum-based chemotherapies who responded to their last platinum-based therapy were enrolled in ARIEL3 and randomized 2:1 to rucaparib 600 mg twice daily or placebo. Exploratory, post hoc analyses of progression-free survival (PFS), patient-centered outcomes (quality-adjusted PFS [QA-PFS] and quality-adjusted time without symptoms or toxicity [Q-TWiST]), and safety were conducted in three age subgroups (<65 years, 65-74 years, and ≥75 years). RESULTS:Investigator-assessed PFS was significantly longer with rucaparib than placebo in patients aged <65 years (rucaparibn = 237 vsplacebo n = 117; median, 11.1 vs 5.4 months; hazard ratio [HR]: 0.33 [95% confidence interval (95% CI) 0.25-0.43]; P < 0.0001) and 65-74 years (n = 113 vs n = 64; median, 8.3 vs 5.3 months; HR 0.43 [95% CI 0.29-0.63]; P < 0.0001) and numerically longer in patients aged ≥75years (n = 25 vs n = 8; median, 9.2 vs 5.5 months; HR 0.47 [95% CI 0.16-1.35]; P = 0.1593). QA-PFS and Q-TWiST were significantly longer with rucaparib than placebo across all age subgroups. Safety of rucaparib was generally similar across the age subgroups. CONCLUSIONS:Efficacy, patient-centered outcomes, and safety of rucaparib were similar between age subgroups, indicating that all eligible women with recurrent ovarian cancer should be offered this therapeutic option, irrespective of age. https://clinicaltrials.gov/ct2/show/NCT01968213.
RCT Entities:
BACKGROUND: In the phase 3 trial ARIEL3, maintenance treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib provided clinical benefit versus placebo for patients with recurrent, platinum-sensitive ovarian cancer. Here, we evaluate the impact of age on the clinical utility of rucaparib in ARIEL3. METHODS:Patients with platinum-sensitive, recurrent ovarian carcinoma with ≥2 prior platinum-based chemotherapies who responded to their last platinum-based therapy were enrolled in ARIEL3 and randomized 2:1 to rucaparib 600 mg twice daily or placebo. Exploratory, post hoc analyses of progression-free survival (PFS), patient-centered outcomes (quality-adjusted PFS [QA-PFS] and quality-adjusted time without symptoms or toxicity [Q-TWiST]), and safety were conducted in three age subgroups (<65 years, 65-74 years, and ≥75 years). RESULTS: Investigator-assessed PFS was significantly longer with rucaparib than placebo in patients aged <65 years (rucaparib n = 237 vs placebo n = 117; median, 11.1 vs 5.4 months; hazard ratio [HR]: 0.33 [95% confidence interval (95% CI) 0.25-0.43]; P < 0.0001) and 65-74 years (n = 113 vs n = 64; median, 8.3 vs 5.3 months; HR 0.43 [95% CI 0.29-0.63]; P < 0.0001) and numerically longer in patients aged ≥75 years (n = 25 vs n = 8; median, 9.2 vs 5.5 months; HR 0.47 [95% CI 0.16-1.35]; P = 0.1593). QA-PFS and Q-TWiST were significantly longer with rucaparib than placebo across all age subgroups. Safety of rucaparib was generally similar across the age subgroups. CONCLUSIONS: Efficacy, patient-centered outcomes, and safety of rucaparib were similar between age subgroups, indicating that all eligible women with recurrent ovarian cancer should be offered this therapeutic option, irrespective of age. https://clinicaltrials.gov/ct2/show/NCT01968213.
Authors: Andrew R Clamp; Domenica Lorusso; Amit M Oza; Carol Aghajanian; Ana Oaknin; Andrew Dean; Nicoletta Colombo; Johanne I Weberpals; Giovanni Scambia; Alexandra Leary; Robert W Holloway; Margarita Amenedo Gancedo; Peter C Fong; Jeffrey C Goh; David M O'Malley; Deborah K Armstrong; Susana Banerjee; Jesus García-Donas; Elizabeth M Swisher; Terri Cameron; Sandra Goble; Robert L Coleman; Jonathan A Ledermann Journal: Int J Gynecol Cancer Date: 2021-06-08 Impact factor: 4.661