Progression-free survival and safety at 3.5years of follow-up: results from the randomised phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer

Antonio González-Martín; Bhavana Pothuri; Ignace Vergote; Whitney Graybill; Domenica Lorusso; Colleen C McCormick; Gilles Freyer; Floor Backes; Florian Heitz; Andrés Redondo; Richard G Moore; Christof Vulsteke; Roisin E O'Cearbhaill; Izabela A Malinowska; Luda Shtessel; Natalie Compton; Mansoor R Mirza; Bradley J Monk

doi:10.1016/j.ejca.2023.04.024

Progression-free survival and safety at 3.5years of follow-up: results from the randomised phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer

Eur J Cancer. 2023 Aug:189:112908. doi: 10.1016/j.ejca.2023.04.024. Epub 2023 May 3.

Authors

Antonio González-Martín¹, Bhavana Pothuri², Ignace Vergote³, Whitney Graybill⁴, Domenica Lorusso⁵, Colleen C McCormick⁶, Gilles Freyer⁷, Floor Backes⁸, Florian Heitz⁹, Andrés Redondo¹⁰, Richard G Moore¹¹, Christof Vulsteke¹², Roisin E O'Cearbhaill¹³, Izabela A Malinowska¹⁴, Luda Shtessel¹⁴, Natalie Compton¹⁴, Mansoor R Mirza¹⁵, Bradley J Monk¹⁶

Affiliations

¹ Medical Oncology Department, Cancer Center Clínica Universidad de Navarra, Madrid, Program in Solid Tumours, CIMA, Pamplona, and Grupo Español de Investigación en Cáncer de Ovario (GEICO), Madrid, Spain.
² Gynecologic Oncology Group (GOG Foundation), NYU Langone, Health, Department of Obstetrics & Gynecology, Perlmutter Cancer Center, New York, NY, USA.
³ Belgium and Luxembourg Gynaecological Oncology Group (BGOG), Department of Gynaecology and Obstetrics, Division of Gynaecological Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium.
⁴ GOG, Gynecologic Oncology, Medical University of South Carolina, Charleston, SC, USA.
⁵ Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies (MITO), Fondazione Policlinico Gemelli IRCCS and Catholic University of Sacred Heart, Rome, Italy.
⁶ GOG, Legacy Medical Group Gynecologic Oncology, Portland, OR, USA.
⁷ Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), HCL Cancer Institute Department of Medical Oncology, Lyon University, Lyon, France.
⁸ Division of Gynecologic Oncology, Ohio State University, Columbus, OH, USA.
⁹ AGO Study Group and the Department for Gynaecology and Gynaecologic Oncology, Kliniken Essen-Mitte, Essen, Germany; Charité - Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Department of Gynaecology, Berlin, Germany.
¹⁰ GEICO, Department of Medical Oncology, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
¹¹ Division of Gynecologic Oncology, Wilmot Cancer Institute, Department of Obstetrics and Gynecology, University of Rochester, Rochester, NY, USA.
¹² BGOG, Department of Medical Oncology and Hematology, AZ Maria Middelares, Gent, Belgium; Department of Molecular Imaging, Pathology, Radiotherapy & Oncology, Center for Oncological Research, Antwerp University, Antwerp, Belgium.
¹³ GOG, Gynecologic Medical Oncology, Memorial Sloan Kettering Cancer Center, and Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
¹⁴ GSK, Middlesex, UK.
¹⁵ Department of Oncology, Rigshospitalet-Copenhagen University Hospital and Nordic Society of Gynaecological Oncology, Copenhagen, Denmark.
¹⁶ HonorHealth Research Institute, University of Arizona College of Medicine, Phoenix Creighton University, Phoenix, AZ, USA.

PMID: 37263896
DOI: 10.1016/j.ejca.2023.04.024

Abstract

Purpose: To report updated long-term efficacy and safety from the double-blind, placebo-controlled, phase 3 PRIMA/ENGOT-OV26/GOG-3012 study (NCT02655016).

Methods: Patients with newly diagnosed advanced ovarian cancer with complete or partial response (CR or PR) to first-line platinum-based chemotherapy received niraparib or placebo once daily (2:1 ratio). Stratification factors were best response to first-line chemotherapy regimen (CR/PR), receipt of neoadjuvant chemotherapy (yes/no), and homologous recombination deficiency (HRD) status (deficient [HRd]/proficient [HRp] or not determined). Updated (ad hoc) progression-free survival (PFS) data (as of November 17, 2021) by investigator assessment (INV) are reported.

Results: In 733 randomised patients (niraparib, 487; placebo, 246), median PFS follow-up was 3.5years. Median INV-PFS was 24.5 versus 11.2months (hazard ratio, 0.52; 95% confidence interval [CI], 0.40-0.68) in the HRd population and 13.8 versus 8.2months (hazard ratio, 0.66; 95% CI, 0.56-0.79) in the overall population for niraparib and placebo, respectively. In the HRp population, median INV-PFS was 8.4 versus 5.4months (hazard ratio, 0.65; 95% CI, 0.49-0.87), respectively. Results were concordant with the primary analysis. Niraparib-treated patients were more likely to be free of progression or death at 4years than placebo-treated patients (HRd, 38% versus 17%; overall, 24% versus 14%). The most common grade ≥ 3 treatment-emergent adverse events in niraparib patients were thrombocytopenia (39.7%), anaemia (31.6%), and neutropenia (21.3%). Myelodysplastic syndromes/acute myeloid leukaemia incidence rate (1.2%) was the same for niraparib- and placebo-treated patients. Overall survival remained immature.

Conclusions: Niraparib maintained clinically significant improvements in PFS with 3.5years of follow-up in patients with newly diagnosed advanced ovarian cancer at high risk of progression irrespective of HRD status. No new safety signals were identified.

Keywords: Advanced ovarian cancer; Maintenance therapy; Niraparib; PARP inhibitor.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Ovarian Epithelial / drug therapy
Female
Humans
Indazoles / adverse effects
Maintenance Chemotherapy / methods
Ovarian Neoplasms* / drug therapy
Progression-Free Survival

Substances

niraparib
Indazoles

Associated data

ClinicalTrials.gov/NCT02655016