Niraparib Versus Bevacizumab as Maintenance Therapy in Patients With de Novo Ovarian Cancer Without Homologous Recombination Deficiency

NCT ID: NCT06827353

Last Updated: 2025-02-14

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-10-01
• Study Completion Date: 2025-09-30

Brief Summary

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.

Detailed 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.

Conditions

Ovarian Carcinoma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

niraparib

Patients who received niraparib as maintenance therapy

maintenance therapy with niraparib

Intervention Type: DRUG

Maintenance therapy after platine-based chemotherapy in non-mutated advanced ovarian cancer is unclear. Arm of patients that received niraparib after chemotherapy.

bevacizumab

Patients who received bevacizumab as maintenance therapy

maintenance therapy with bevacizumab

Intervention Type: DRUG

Maintenance therapy after platine-based chemotherapy in non-mutated advanced ovarian cancer is unclear. Arm of patients that received bevacizumab after chemotherapy.

Interventions

maintenance therapy with bevacizumab

Maintenance therapy after platine-based chemotherapy in non-mutated advanced ovarian cancer is unclear. Arm of patients that received bevacizumab after chemotherapy.

Intervention Type: DRUG

maintenance therapy with niraparib

Maintenance therapy after platine-based chemotherapy in non-mutated advanced ovarian cancer is unclear. Arm of patients that received niraparib after chemotherapy.

Intervention Type: DRUG

Other Intervention Names

bevacizumab; niraparib

Eligibility Criteria

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

• Disease progression after chemotherapy
• Presence of a BRCA mutation (somatic or germline)
• Positive HRD score

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Nīmes

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

soufyan annakib, M.D.

Role: PRINCIPAL_INVESTIGATOR

Frédéric Fiteni, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire de Nīmes

Locations

CHU de Nîmes

Nîmes, Occitanie, France

Site Status: RECRUITING

Countries

France

Central Contacts

Soufyan Annakib, M.D.

Role: CONTACT

soufyan.annakib@gmail.com

+33466683301

Sabrina Nicolas

Role: CONTACT

sabrina.nicolas@chu-nimes.fr

Facility Contacts

Sarah Kabani

Role: primary

sarah.kabani@chu-nimes.fr

+33466684175

References

Hannaway N, Kassaris S, Davies JM, Smrke A, Tinker A, Drew Y. Using chemotherapy response by KELIM score to predict response to first line maintenance PARP inhibitor therapy in non-BRCA mutant/homologous recombination deficiency (HRD) unknown high grade serous ovarian cancer (HGSOC). J Clin Oncol. 1 juin 2023;41(16_suppl):e17547-e17547.

Reference Type: BACKGROUND

Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, Mannel RS, Homesley HD, Fowler J, Greer BE, Boente M, Birrer MJ, Liang SX; Gynecologic Oncology Group. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med. 2011 Dec 29;365(26):2473-83. doi: 10.1056/NEJMoa1104390.

Reference Type: BACKGROUND

PMID: 22204724 (View on PubMed)

Gonzalez-Martin A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O'Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Perez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2391-2402. doi: 10.1056/NEJMoa1910962. Epub 2019 Sep 28.

Reference Type: BACKGROUND

PMID: 31562799 (View on PubMed)

Gonzalez-Martin A, Harter P, Leary A, Lorusso D, Miller RE, Pothuri B, Ray-Coquard I, Tan DSP, Bellet E, Oaknin A, Ledermann JA; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Newly diagnosed and relapsed epithelial ovarian cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023 Oct;34(10):833-848. doi: 10.1016/j.annonc.2023.07.011. Epub 2023 Aug 17. No abstract available.

Reference Type: BACKGROUND

PMID: 37597580 (View on PubMed)

Defossez G, le Guyader-Peyrou S, Uhry Z. Estimations nationales de l'incidence et de la mortalité par cancer en France métropolitaine entre 1990 et 2018. Saint-Maurice (Fra): Santé publique France; 2019.

Reference Type: BACKGROUND

Other Identifiers

24.10.24

Identifier Type: -

Identifier Source: org_study_id