| Institution: | 1. NSGO and Rigshospitalet–Copenhagen University Hospital, Copenhagen, Denmark;2. Medical Oncology Department, Grupo Español de Investigación en Cáncer de Ovario (GEICO), Clínica Universidad de Navarra, Madrid, Spain
Program in Solid Tumors, Center for Applied Medical Research (CIMA), Pamplona, Spain;3. GOG and Gynecologic Oncology, Medical University of South Carolina, Charleston, South Carolina, USA;4. James Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, USA;5. Medical Oncology Department, Hospital Clinic de Barcelona, Translational Genomics and Targeted Therapies in Solid Tumors, Institut D'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain;6. University Gynecologic Oncology, Atlanta, Georgia, USA;7. Hospital Universitario Ramón y Cajal, Madrid, Spain;8. Cleveland Clinic, Cleveland, Ohio, USA;9. Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium;10. Georgia Cancer Center, Augusta University, Augusta, Georgia, USA;11. Ghent University Hospital, Ghent, Belgium;12. Minnesota Oncology, Minneapolis, Minnesota, USA;13. Istituto Nazionale Tumori IRCCS Fondazione Pascale, Naples, Italy;14. Centre Antoine Lacassagne, Nice, France;15. Arbeitsgemeinschaft Gynäkologische Onkologie and the Department of Gynecology and Obstetrics, Klinikum der Stadt Ludwigshafen, Ludwigshafen, Germany;16. Cancer Trials Ireland, Dublin, Ireland;17. Gynecologic Oncology Department, Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;18. GSK, Waltham, Massachusetts, USA;19. HonorHealth Research Institute, University of Arizona College of Medicine, Creighton University School of Medicine, Phoenix, Arizona, USA |
| Abstract: | Background The PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) trial was amended to prospectively evaluate the safety and efficacy of an individualized starting dose (ISD) regimen of niraparib for first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer. Methods In the phase 3 PRIMA trial, patients with newly diagnosed advanced ovarian cancer with a complete/partial response to first-line platinum-based chemotherapy (N = 733) were initially treated with a fixed starting dose (FSD) regimen of 300 mg once daily. Subsequently, the protocol was amended so newly enrolled patients received an ISD: 200 mg once daily in patients with baseline body weight < 77 kg or baseline platelet count < 150,000/µL, and 300 mg once daily in all other patients. Efficacy and safety outcomes were assessed by starting dose. Results Overall, 475 (64.8%) patients were assigned to an FSD (niraparib, n = 317; placebo, n = 158) and 258 (35.2%) were assigned to an ISD (niraparib, n = 170; placebo, n = 88). Efficacy in patients who received FSD or ISD was similar for the overall (FSD hazard ratio HR], 0.59 95% CI, 0.46–0.76] vs. ISD HR, 0.69 95% CI, 0.48–0.98]) and the homologous recombination–deficient (FSD HR, 0.44 95% CI, 0.30–0.64] vs. ISD HR, 0.39 95% CI, 0.22–0.72]) populations. In patients with low body weight/platelet count, rates of grades ≥3 and 4 hematologic treatment-emergent adverse events, dose interruptions, and dose reductions were lower for those who received ISD than for those who received FSD. Conclusions In PRIMA, similar dose intensity, similar efficacy, and improved safety were observed with the ISD compared with the FSD regimen. |
