Dostarlimab/Chemo, Maintenance Niraparib Show Modest Improvements in Ovarian Cancer

The median PFS with dostarlimab plus niraparib was 20.6 months vs 19.2 months with niraparib alone in patients with treatment-naive advanced ovarian cancer.

First-line treatment with dostarlimab-gxly (Jemperli) plus platinum-based chemotherapy and maintenance niraparib (Zejula) demonstrated a statistically significant, though clinically modest, improvement in progression-free survival (PFS) and an expected safety profile in patients with newly diagnosed advanced ovarian cancer, based on results from the phase 3 FIRST/ENGOT-OV44 trial (NCT03602859) shared at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

Results from the trial were concurrently published in Annals of Oncology.²

The median PFS with dostarlimab plus niraparib was 20.6 months (95% CI, 19.2-22.8) vs 19.2 months (95% CI, 16.6-21.0) with niraparib alone (HR, 0.85; 95% CI, 0.73-0.99; P = .0351); the 1-year PFS rates were 75% vs 70%, 2-year PFS rates were 44% vs 40%, and 3-year PFS rates were 32% vs 27%.

In patients with PD-L1–positive tumors, defined as a tumor area positivity of 5% or greater, the median PFS was 28.1 months (95% CI, 22.3-37.8) with the combination vs 24.3 months (95% CI, 19.6-39.6) with niraparib alone (HR, 0.84; 95% CI, 0.61-1.17). The 1-year PFS rates were 78% vs 77%, 2-year PFS rates were 55% vs 51%, and 3-year PFS rates were 44% vs 41%.

PFS subgroup analyses showed 66% of the combination arm and 68% of the monotherapy arm with the primary peritoneal as the primary tumor site experienced a PFS event (HR, 1.02; 95% CI, 0.62-1.66), and 53% and 50% of patients, respectively, with the fallopian tubes as the primary tumor site experienced a PFS event (HR, 1.17; 95% CI, 0.68-2.01); 78% and 75% of those with nonsurgical status at screening experienced a PFS event (HR, 1.17; 95% CI, 0.74-1.84).

Additionally, 42% and 46%, respectively, of those with BRCA-mutated disease experienced a PFS event (HR, 0.98; 95% CI, 0.65-1.48), and 52% vs 72% of those with homologous recombination deficiency (HRD) experienced a PFS event (HR, 0.68; 95% CI, 0.48-0.96).

The median overall survival (OS) was 44.4 months (95% CI, 41.2-47.5) with the combination vs 45.4 months (95% CI, 40.4-52.2) with niraparib alone (HR, 1.01; 95% CI, 0.86-1.19; P = .906).

Kathleen N. Moore, MD, MS, a professor and associate director of clinical research at Stephenson Cancer Center at The University of Oklahoma College of Medicine in Oklahoma City, and coauthors noted in the presentation, “The addition of dostarlimab to first-line platinum-based chemotherapy and maintenance niraparib was associated with a statistically significant, though clinically modest, improved PFS for patients with newly diagnosed [advanced ovarian cancer].”¹

A total of 1162 patients were randomly assigned 1:2 to receive carboplatin/paclitaxel chemotherapy plus placebo with or without bevacizumab (Avastin), or carboplatin/paclitaxel chemotherapy plus dostarlimab with or without bevacizumab. Maintenance treatment was niraparib plus placebo with or without bevacizumab, or niraparib plus dostarlimab with or without bevacizumab.

Eligible patients were 18 years or older with high-grade nonmucinous epithelial ovarian cancer and stage IV disease or stage III if: stage IIIC with CC0 resection during primary debulking surgery, inoperable disease, macroscopic residual tumor after primary debulking surgery, or planned neoadjuvant chemotherapy. It was noted that the primary debulking strategy, the interval debulking strategy, and patients who were inoperable were all included.

The trial’s primary end point was PFS per RECIST v1.1, and if PFS was statistically significant, testing would continue to OS. Patients with PD-L1-positive or HRD tumors and those with concurrent bevacizumab were labeled a priori as groups that may have differentiated results.

Results from the EuroQol Visual Analogue Scale and EORTC QLQ-C30 assessments showed that patients who received the combination and the monotherapy were stable in their health-related quality of life, functioning, and symptoms, without clinically meaningful worsening.

It was noted that treatment was discontinued due to adverse events (AEs) in 16% of the combination group and 8% of the monotherapy group; progressive disease in 49% and 83%; patient request in 10% and 8%; and death in 2% and less than 1%, respectively.

In the chemotherapy period, any treatment-related AEs (TRAEs) occurred in 94.4% and 92.6% of the combination group and the monotherapy group, respectively; any grade 3 or higher TRAEs occurred in 41.1% and 37.2%. In the maintenance period, any TRAEs occurred in 97.1% and 94.6% of patients, respectively; any grade 3 or higher TRAEs occurred in 70.2% and 64.7%.

In the overall study period, the most common any-grade treatment-emergent AEs were anemia (62.3% vs 62.1%), nausea (50.1% vs 50.8%), constipation (37.7% vs 38.1%), and fatigue (36.8% vs 29.5%).

Any treatment-related immune-related AE occurred in 38.4% of the combination group and 13.9% of the monotherapy group; they included hypothyroidism (12.5% vs 1.7%), arthralgia (4.8% vs 4.3%), and rash (4.8% vs 0.7%).

“Further research into identifying patients who may benefit from the FIRST regimen is warranted,” the authors concluded in the paper.²

Reference

1. Hardy-Bessard AC, Pujade-Lauraine E, Moore RG, et al. FIRST/ENGOT-OV44: a phase 3 clinical trial of dostarlimab (dost) and niraparib (nira) in first-line (1L) advanced ovarian cancer (aOC). Presented at: 2025 American Society of Clinical Oncology Annual Meeting. May 30-June 3, 2025. Chicago, IL. LBA5506.
2. Hardy-Bessard AC, Pujade-Lauraine E, Moore RG, et al. Dostarlimab and niraparib in primary advanced ovarian cancer. Ann Oncol. Published online June 2, 2025. doi:10.1016/j.annonc.2025.05.009