Frontline Maintenance With Niraparib Plus Bevacizumab Is Active in Advanced Ovarian Cancer

The combination of niraparib (Zejula) and bevacizumab (Avastin) led to durable overall survival (OS) without adversely affecting health-related quality of life (HRQOL) as maintenance therapy in patients with newly diagnosed advanced ovarian cancer that responded to frontline platinum-based chemotherapy, according to updated data from the phase 2 OVARIO trial (NCT03326193) presented during the 2025 SGO Annual Meeting on Women’s Cancer.1

At a data cutoff date of August 12, 2024, and median follow-up of 65.7 months, the median OS was 61.1 months (95% CI, 44.9-not evaluable [NE]) in the overall population (n = 105). The data maturity for OS was 52.4%.

“Overall results were consistent with known findings for PARP inhibitor plus bevacizumab combination maintenance treatment,” Melissa M. Hardesty, MD, lead study author and managing partner at Alaska Women’s Cancer Center in Anchorage, Alaska, and coauthors wrote in the poster. “Subgroup data by homologous recombination deficiency and BRCA status should be interpreted with caution given the small number of patients.”

Surgery and platinum-based chemotherapy is the standard of care for patients with primary advanced ovarian cancer. If complete or partial response is achieved with frontline chemotherapy, patients may also receive maintenance therapy with a PARP inhibitor alone or in combination with bevacizumab.

Niraparib is currently approved for use as maintenance monotherapy in patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy.2 Approval was based on data from the phase 3 PRIMA trial (NCT02655016) in which niraparib led to a significant improvement in progression-free survival (PFS) vs placebo in this setting (HR, 0.43; 95% CI, 0.31-0.59; P <.0001). OS benefit was not seen with subsequent follow-up, with median values of 46.6 months and 48.8 months in the niraparib and placebo arms, respectively (HR, 1.01; 95% CI, 0.84-1.23; P =.8834).3

OVARIO is a US-based, phase 2, single-arm, open-label trial that evaluated the combination of niraparib and bevacizumab as maintenance therapy for patients with newly diagnosed advanced ovarian cancer that responded to frontline platinum-based chemotherapy.1

The study enrolled patients with newly diagnosed, high-grade serous or endometrioid stage IIIB or IV epithelial ovarian, fallopian tube, or peritoneal cancer who achieved a complete response, partial response, or no evidence of disease result after frontline platinum-based chemotherapy plus bevacizumab.

Patients received 200 mg (n = 82; 78.1%) or 300 mg (n = 23; 21.9%) of niraparib once daily dependent on baseline weight, plus 15 mg/kg of bevacizumab once every 3 weeks. All patients underwent tissue testing for homologous recombination–deficiency (HRD) status at enrollment.

The primary end point was the 18-month PFS rate. Secondary end points included OS, time to first subsequent therapy, time to second subsequent therapy, safety, patient-reported outcomes (PROs), and RECIST or CA-125 PFS.

A total of 105 patients were included in the efficacy and safety analysis population, all of whom have discontinued treatment with both agents. Of these patients, 49 had HRD, 38 had homologous recombination proficiency (HRP), and 18 had homologous recombination not determined (HRnd).

The median age was 60 years (IQR, 54-67); 21.9% of patients had stage IV disease at diagnosis and 63.8% had BRCA wild-type disease. In the overall population, 73.3% of patients received 1 (21.4%), 2 (14.3%), 3 (10.5%), or 4 or more (17.1%) lines of subsequent anticancer therapy. Subsequent therapies included surgery (12.4%), radiotherapy (10.5%), platinum-based chemotherapy (60.0%), bevacizumab or bevacizumab biosimilar (39.0%), taxane (41.9%), doxorubicin (54.3%), gemcitabine (32.4%), or PARP inhibitor (30.5%).

Findings from the primary analysis, which were presented after a median follow-up of 28.7 months, demonstrated that the median PFS was 19.6 months (95% CI, 16.5-25.1) in the overall population (n = 105). The median PFS in the HRD, HRP, and HRnd populations was 28.3 months (95% CI, 19.9-NE), 14.2 months (95% CI, 8.6-16.8), and 12.1 months (95% CI, 8.0-NE), respectively.4

Additional data from the updated analysis illustrated OS outcomes according to biomarker status.1 The median OS in the overall HRD population (n = 49) was NE (95% CI, 58.2-NE). Among those with BRCA-mutant (n = 29) and wild-type (n = 16) disease the median OS was 68.3 months (95% CI, 52.5-NE) and NE (95% CI, 38.6-NE), respectively. The median OS in the HRP population (n = 38) was 38.7 months (95% CI, 21.9-63.8). In the HRnd population (n = 18) the median OS was 39.8 months (95% CI, 21.7-NE). Finally, in the BRCA-mutant (n = 29) and wild-type (n = 67) populations the median OS was 68.3 months (95% CI, 52.5-NE) and 53.5 months (95% CI, 33.5-NE), respectively.

Safety findings were largely consistent with those from the primary analysis, although 4 new primary malignancies were reported.

Serious treatment-related adverse effects (TRAEs) occurred in 19.0% of patients; 17.1% were niraparib related and 6.7% were bevacizumab related. TRAEs leading to discontinuation of any study treatment occurred in 43.8% of patients; 29.5% and 28.6% of events led to niraparib and bevacizumab discontinuations, respectively. TRAEs leading to treatment interruption occurred in 88.6% of patients; niraparib dose interruptions and reductions were required in 88.6% and 77.1% of cases, respectively, vs 3.8% and 52.4% of bevacizumab cases, respectively. No TRAEs led to death.

Niraparib-related TRAEs included fatigue (55.2%), anemia (49.5%), nausea (49.5%), decreased platelet count (40.0%), thrombocytopenia (34.3%), hypertension (34.3%), headache (24.8%), vomiting (18.1%), decreased white blood cell count (17.1%), dyspnea (16.2%), decreased neutrophil count (13.3%), constipation (13.3%), decreased appetite (12.4%), neutropenia (12.4%), stomatitis (10.5%), arthralgia (10.5%), insomnia (10.5%), epistaxis (8.6%), and proteinuria (3.8%).

Any grade 3 or greater TRAEs occurred in 80.0% of patients. Any grade 3 or greater TRAEs included fatigue (9.5%), anemia (34.3%), nausea (1.0%), decreased platelet count (22.9%), thrombocytopenia (19.0%), hypertension (25.7%), headache (5.7%), vomiting (1.0%), decreased white blood cell count (1.0%), dyspnea (1.0%), decreased neutrophil count (4.8%), neutropenia (7.6%), stomatitis (3.8%), arthralgia (1.9%), insomnia (1.9%), and proteinuria (4.8%).

With respect to PROs, the combination did not adversely affect HRQOL according to the Functional Assessment of Cancer Therapy––Ovarian Symptom Index. The median durations of bevacizumab and niraparib exposure were 9.0 months (range, 0.7-24.0) and 12.4 months (range, 0.4-70.2), respectively.

Disclosures: Hardesty reports consulting fees from AstraZeneca, Daiichi Sankyo, Eisai, GSK, ImmunoGen/AbbVie, MSD, Takeda, and Yanuvia; speaker fees from MSD; and uncompensated membership on the National Ovarian Cancer Coalition (NOCC) Medical & Scientific Advisory Board and various committees of the Society of Gynecologic Oncology (SGO).

References

1. Hardesty MM, Krivak TC, Wright GS, et al. A phase 2 study of niraparib plus bevacizumab maintenance following front-line platinum-based chemotherapy with bevacizumab in advanced ovarian cancer: final analysis from the OVARIO study. Presented at: 2025 SGO Annual Meeting on Women’s Cancer; March 14-17, 2025; Seattle, WA. Abstract 836266.
2. FDA approves niraparib for first-line maintenance of advanced ovarian cancer. FDA. April 29, 2020. Accessed March 16, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-niraparib-first-line-maintenance-advanced-ovarian-cancer
3. González-Martín A, Pothuri B, Barretina Ginesta MP, et al. Final overall survival (OS) in patients (pts) with newly diagnosed advanced ovarian cancer (aOC) treated with niraparib (nir) first-line (1L) maintenance: results from PRIMA/ENGOT-OV26/GOG-3012. Ann Oncol. 2024;35(suppl 2):S1222-S1223. doi:10.1016/j.annonc.2024.08.2268
4. Hardesty MM, Krivak TC, Wright GS, et al. OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab. Gynecol Oncol. 2022;166(2):219-229. doi:10.1016/j.ygyno.2022.05.020