Ad hoc Analysis of the Phase III ENGOT-OV16/NOVA Study: Niraparib Efficacy in Germline BRCA Wild-type Recurrent Ovarian Cancer with Homologous Recombination Repair Defects

Mansoor Raza Mirza, Nordic Society of Gynaecological Oncology (NSGO) and Department of Oncology Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark.
Gabriel Lindahl, Nordic Society of Gynaecological Oncology (NSGO) and Department of Oncology, Linköping University Hospital, Linköping, Sweden.
Sven Mahner, Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe (AGO) and Department of Gynecology and Gynecologic Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Andrés Redondo, Grupo Español de Investigación en Cáncer de Ovario (GEICO) and Department of Medical Oncology, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
Michel Fabbro, ICM Val d'Aurelle Parc Euromedecine, Oncologie Médicale, Montpellier, GINECO, Paris, France.
Bobbie J. Rimel, Cedars-Sinai Cancer, Cedars-Sinai Medical Center, Los Angeles, California.
Jørn Herrstedt, Department of Clinical Oncology and Palliative Care Zealand University Hospital Roskilde and Næstved, University of Copenhagen, Copenhagen, Denmark.
Amit M. Oza, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Ulrich Canzler, Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe (AGO) and Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Jonathan S. Berek, Stanford University School of Medicine and Stanford Cancer Institute, Stanford, California.
Antonio González-Martín, Medical Oncology Department, Clínica Universidad de Navarra, Madrid, Program in Solid Tumors, Center for Applied Medical Research (CIMA), Pamplona, Spain, Grupo Español de Investigación en Cáncer de Ovario (GEICO), Madrid, Spain.
Phillipe Follana, Centre Antoine Lacassagne, Nice, France.
Rosemary Lord, Medical Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Bebington, United Kingdom.
Masoud Azodi, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut.
Kasey Estenson, GSK, Philadelphia, Pennsylvania.
Zebin Wang, GSK, Waltham, Massachusetts.
Yong Li, GSK, Waltham, Massachusetts.
Divya Gupta, GSK, Waltham, Massachusetts.
Ursula Matulonis, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Bin Feng, GSK, Waltham, Massachusetts.

Document Type

Article

Publication Title

Cancer research communications

Abstract

UNLABELLED: In this analysis, we examined the relationship between progression-free survival (PFS) and mutation status of 18 homologous recombination repair (HRR) genes in patients in the non-germline BRCA-mutated (non-gBRCAm) cohort of the ENGOT-OV16/NOVA trial (NCT01847274), which evaluated niraparib maintenance therapy for patients with recurrent ovarian cancer. This post hoc exploratory biomarker analysis was performed using tumor samples collected from 331 patients enrolled in the phase III ENGOT-OV16/NOVA trial's non-gBRCAm cohort. Niraparib demonstrated PFS benefit in patients with either somatic BRCA-mutated (sBRCAm; HR, 0.27; 95% confidence interval, CI, 0.08-0.88) or BRCA wild-type (BRCAwt; HR, 0.47; 95% CI, 0.34-0.64) tumors. Patients with BRCAwt tumors with other non-BRCA HRR mutations also derived benefit from niraparib (HR, 0.31; 95% CI, 0.13-0.77), as did patients with BRCAwt/HRRwt (HRR wild-type) tumors (HR, 0.49; 95% CI, 0.35-0.70). When patients with BRCAwt/HRRwt tumors were further categorized by genomic instability score (GIS), clinical benefit was observed in patients with homologous recombination-deficient (GIS ≥ 42; HR, 0.33; 95% CI, 0.18-0.61) and in patients with homologous recombination-proficient (HRp; GIS < 42; HR, 0.60; 95% CI, 0.36-0.99) disease. Although patients with sBRCAm, other non-BRCA HRR mutations, or GIS ≥ 42 benefited the most from niraparib treatment, PFS benefit was also seen in HRp (GIS < 42) patients without HRR mutations. These results support the use of niraparib in patients with recurrent ovarian cancer regardless of BRCA/HRR mutation status or myChoice CDx GIS. SIGNIFICANCE: We retrospectively evaluated the mutational profile of HRR genes in tumor samples from 331 patients from the non-germline BRCA-mutated cohort of the phase III NOVA trial of patients with platinum-sensitive high-grade serous ovarian cancer. Patients with non-BRCA HRR mutations generally benefited from second-line maintenance treatment with niraparib compared with placebo.

First Page

1436

Last Page

1444

DOI

10.1158/2767-9764.CRC-22-0240

Publication Date

11-1-2022

Identifier

36970052 (pubmed); PMC10035404 (pmc); 10.1158/2767-9764.CRC-22-0240 (doi); CRC-22-0240 (pii)

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