LBA3_PR - A randomized, double-blind phase 3 trial of maintenance therapy with niraparib vs placebo in patients with platinum-sensitive recurrent ovarian can...

Date 08 October 2016
Event ESMO 2016 Congress
Session Presidential Symposium 1
Topics Ovarian Cancer
Presenter Mansoor Raza Mirza
Citation Annals of Oncology (2016) 27 (6): 1-36. 10.1093/annonc/mdw435
Authors M.R. Mirza1, B.J. Monk2, A. Oza3, S. Mahner4, A. Redondo5, M. Fabbro6, J. Ledermann7, D. Lorusso8, I.B. Vergote9, O. Rosengarten10, J. Berek11, J. Herrstedt12, A.V. Tinker13, A. Dubois14, A. Gonzalez Martin15, P. Follana16, B. Benigno17, B.J. Rimel18, S. Agarwal19, U. Matulonis20
  • 1Department Of Oncology 5073, NSGO & Rigshospitalet-Copenhagen University Hospital, 2100 - Copenhagen/DK
  • 2Department Of Oncology, University of Arizona Cancer Center-Phoenix, Phoenix/US
  • 3Department Of Oncology, University Health Network, Toronto/CA
  • 4Department Of Gynegology, AGO & University of Munich, Hamburg/DE
  • 5Department Of Oncology, GEICO & Hospital Universitario, Madrid/ES
  • 6Department Of Oncology, GINECO & Institut du Cancer de Montpellier, Montpellier/FR
  • 7Department Of Medical Oncology, NCRI & University College London, London/GB
  • 8Department Of Gynecologic Oncology, MITO/MaNGO & Fondazione IRCCS National Cancer Institute, Milano/IT
  • 9Department Of Obstetrics And Gynecology, BGOG & University of Leuven, Leuven/BE
  • 10Department Of Gynecologic Oncology, ISGO & Sha’are Zedek Medical Center, Jerusalem/IL
  • 11Department Of Oncology, Stanford Women’s Cancer Center, Stanford/US
  • 12Department Of Oncology, NSGO & Odense University Hospital, Odense/DK
  • 13Department Of Medicine, British Columbia Cancer Agency, Vancouver/CA
  • 14Department Of Oncology, AGO & Kliniken Essen Mitte, Essen/DE
  • 15Medical Oncology Department, GEICO & MD Anderson Cancer Center Madrid, Madrid/ES
  • 16Department Of Medical Oncology, GINECO & Centre Antoine Lacassagne, Nice/FR
  • 17Department Of Gynecologic Oncology, University Gynecologic Oncology, Atlanta/US
  • 18Department Of Obstetrics And Gynecology, Cedars-Sinai Medical Center, West Hollywood/US
  • 19Department Of Medical Affairs, Tesaro, Inc, 02451 - Waltham/US
  • 20Department Of Gynecologic Oncology, Dana-Farber Cancer Institute, Boston/US

Abstract

Background

Niraparib is an oral, highly selective inhibitor of PARP1/2. This is the first randomized phase 3 trial of a PARP inhibitor as maintenance therapy post-platinum chemotherapy in patients (pts) with platinum-sensitive recurrent ovarian cancer.

Methods

Two independent cohorts were enrolled based on results of BRACAnalysis® testing: pts with a germline BRCA mutation (gBRCAmut), and pts who lacked these mutations (non-gBRCAmut). Within each cohort, pts were randomized (2:1) to receive niraparib 300 mg or placebo once daily. Three prospectively-defined populations were assessed: 1) the gBRCAmut cohort; 2) those in the non-gBRCAmut cohort whose tumors were retrospectively defined as deficient in homologous recombination (HRD) by the myChoice® HRD test; 3) the overall non-gBRCAmut cohort.

Results

553 pts were enrolled in this international trial. 60% of pts had 2 lines of prior therapy, and 40% of pts had >2 prior lines. 76% of pts had stage IIIc or IV disease. Niraparib prolonged progression-free survival (PFS) as compared to placebo in all three pt populations (Table 1). Secondary endpoints of chemotherapy-free interval (CFI), time to first subsequent treatment (TFST), and PFS 2 also showed statistically significant improvement. Patient-reported outcomes (PRO) were similar for niraparib and placebo. Most common (≥10%) treatment-emergent grade 3/4 adverse events in niraparib-treated pts were thrombocytopenia (28%), anaemia (25%), and neutropenia (11%). There were no deaths during study treatment.

Progression-free Survival

gBRCAmut n = 203 non-gBRCAmut n = 350 non-gBRCAmut HRDpos n = 162
Niraparib n = 138 Placebo n = 65 Niraparib n = 234 Placebo n = 116 Niraparib n = 106 Placebo n = 56
PFS Median, Months (95% CI) 21.0 (12.9, NR) 5.5 (3.8, 7.2) 9.3 (7.2, 11.2) 3.9 (3.7, 5.5) 12.9 (8.1, 15.9) 3.8 (3.5, 5.7)
p value

Conclusions

Niraparib significantly improved PFS for all study populations as well as significantly prolonging CFI, TFST and PFS 2 with a manageable safety profile and without adversely impacting PRO.

Clinical trial identification

NCT01847274

Legal entity responsible for the study

Tesaro Inc.

Funding

Tesaro, Inc.

Disclosure

B.J. Monk: Consultant for GSK, Merck, Tesaro, Genentech, AZ, Gradalis, Advaxis, Verastem, Cerulean, Amgen, Vermillion, Immunogen, Bayer, NuCana BioMed, Insys Therapeutics, Clovis Oncology, Oxigene, Pfizer – Speaker for Genentech, AZ, Janssen, Myriad Genetics. A. Oza: Consultant for Amgen, Verastem, Clovis Oncology, Immunovaccine. S. Mahner: Consultant for Roche, AZ, MSD, Jansen-Cilag, Tesaro, Medac – Honorarium from Roche/Genentech, AZ, PharmaMar, Medac, Jenapharm, Janssen-Cilag, Teva, GSK – Research support from Roche, AZ, BI, GSK, Janssen-Cilag, Medac, PharaMar, Tesaro, Bayer. A. Redondo: Consultant for Roche, PharaMar – Honorarium from Roche – Speaker for Roche. M. Fabbro: Has received travel support from Roche. J. Ledermann: Consultant for AZ/MedImmune, Clovis Oncology – Research support from AZ. D. Lorusso: Consultant for AZ, PharaMar, Roche Glycart – Speaker for PharmaMar – travel support from PharaMar, Roche Glycart. I.B. Vergote: Consultant & researcher for AZ, Amgen NV, Array Biopharma, Biogen, BI, BMS, Esai, Lilly, Endocye, Genentech, GSK, Janssen-Cilag, Medimmune, MSD, Morphotek, Nektar, Novo Nordisk, Oasmia, PharaMar, Roche, Sanofi, Shering-Plough, Sigma-Tau, among others. J. Berek: Consultant for Prima BioMed, Atara Biotherapeutics – Research support from Tesaro, Quest Diagnostics, Endocyte, Genentech, AZ, Prima BioMed. J. Herrstedt: Consultant for Tesaro. A.V. Tinker: Consultant for AZ – Research support from AZ/MedImmune. A. Dubois: Consultant for AZ, PharaMar, Roche/Genentech, Mundipharma, Pfizer. A. Gonzalez Martin: Consultant for PharaMar, Roche Glycart, - Speaker for AZ, PharaMar, Roche Glycart P. Follana: Has received travel support from AZ and Roche Glycart. B. Benigno: Consultant for Genentech – Speaker for and received honorarium from AZ, Insys Therapeutics – Travel support from AZ. B.J. Rimel: Consultant for AZ – Received Honorarium from Genentech S. Agarwal: Is an employee of Tesaro. U. Matulonis: Consultant for Merck KGaA, AZ, Immunogen, Tesaro, Genentech. All other authors have declared no conflicts of interest.