Niraparib Versus Bevacizumab As Maintenance Therapy in Patients with De Novo Ovarian Cancer Without Homologous Recombination Deficiency (OVNI-B)

Centre Hospitalier Universitaire de Nīmes

Status

Enrolling

Conditions

Ovarian Carcinoma

Treatments

Drug: maintenance therapy with niraparib

Drug: maintenance therapy with bevacizumab

Study type

Observational

Funder types

Other

Identifiers

NCT06827353

24.10.24

Details and patient eligibility

About

Background: High-grade serous epithelial ovarian cancer is a disease with a poor prognosis in the advanced stages (stages III and IV). For patients with no biomolecular abnormalities, there are two maintenance treatments available after first-line chemotherapy: bevacizumab or niraparib. There is no prospective or strong retrospective study comparing these two therapies.

Hypothesis: Patients receiving bevacizumab are different from those receiving niraparib.

Objective: To compare the progression-free survival (PFS) of patients with high-grade stage III and IV ovarian carcinoma who received chemotherapy with those who received maintenance treatment with bevacizumab and those who received niraparib.

Method: Retrospective, multicenter study based on data collected from the patient's medical record. Eligible patients are all patients diagnosed with de novo high-grade serous epithelial ovarian carcinoma who have received first-line platinum-based chemotherapy followed by maintenance treatment with bevacizumab or niraparib. All eligible patients will be included. Patients with a BRCA mutation and/or a positive HRD score will be excluded. Data will be collected using an electronic CRF. The inclusion period is from October 2020 to December 2023.

Full description

Introduction The incidence of ovarian cancer in France is estimated at over 5,100 cases/year in 2018. The most common histological form is high-grade serous epithelial carcinoma, which accounts for around 70% of ovarian cancers. Mortality is estimated at over 3,400 cases per year. The management of newly-diagnosed patients is based on multimodal treatment with maximal cytoreductive surgery, platinum-based chemotherapy and targeted therapy. For patients with advanced disease (stage III or IV), peri-operative or adjuvant chemotherapy with carboplatin combined with paclitaxel is the standard of treatment. At the end of this treatment, patients benefit from maintenance therapy, which may differ according to their biomolecular characteristics. For patients with a BRCA gene mutation or a high HRD score, the standard treatment is a combination of poly-ADP-ribose-polymerase inhibitor (iPARP) and an anti-VEGF antiangiogenic, bevacizumab.

On the other hand, for patients with no BRCA mutation or with a low HRD score (known as HRP), there are two treatment standards. They can be treated with an iPARP, niraparib. Indeed, the phase III PRIMA trial, which evaluated survival in patients with advanced ovarian cancer regardless of BRCA or HRD status, showed an improvement in progression-free survival (PFS) on an intention-to-treat basis. However, in the population of patients without BRCA and HRP mutations, PFS was 8.1 months in the niraparib group versus 5.4 months in the placebo group. The difference was statistically significant, with a hazard ratio of 0.68 (95% confidence interval 0.49-0.94). Overall survival data were not yet mature in 2023 in the most recent publication.

These same patients may also benefit from maintenance treatment with bevacizumab. A benefit in terms of PFS and OS has been demonstrated for populations at high risk of relapse (stage IV, or non-operable stage III or non-maximal surgery) in the ICON7 phase III study. In the GOG-0218 phase III study, bevacizumab was only shown to benefit progression-free survival.

Thus, both therapeutic strategies can be proposed as maintenance treatment after first-line chemotherapy for patients with advanced high-grade epithelial ovarian carcinoma in the non-mutated BRCA and HRP subpopulation. The data available to help choose between the two molecules are limited. The safety profile of each molecule and the contraindications may help in the choice. In their absence, there are no validated criteria in the scientific literature. The KELIM score (CA-125 ELIMination of Rate Constant K) can be used to predict iPARP efficacy. However, it has not been validated in this indication, since it was originally developed to predict chemosensitivity in these patients. Finally, there are no studies directly comparing the efficacy of bevacizumab with niraparib in this population.

Real-life data are therefore needed to understand and analyze prescribing practices, in order to identify avenues to aid therapeutic choice. Our study therefore aims to describe a population of patients with advanced high-grade epithelial ovarian carcinoma treated with maintenance bevacizumab or niraparib after platinum-based chemotherapy.

Study aim

Main objective:

To compare the progression-free survival (PFS) of patients with high-grade stage III and IV epithelial ovarian carcinoma who received chemotherapy between those who received maintenance treatment with bevacizumab and those who received niraparib.

Secondary objectives A. To describe the OS of the two groups. B. To compare the clinical, biological and sociodemographic characteristics of the two groups.

Enrollment

300 estimated patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

De novo diagnosis of stage III or IV high-grade epithelial ovarian carcinoma, not candidate for primary tumor reduction surgery.
De novo diagnosis of high-grade epithelial ovarian carcinoma benefiting from a combination of chemotherapy and maximal cytoreduction surgery
All patients who have received maintenance treatment after chemotherapy with bevacizumab or niraparib monotherapy.

Exclusion criteria