The phase III FIRST/ENGOT-OV44 trial demonstrated that adding dostarlimab to standard first-line therapy and maintenance niraparib in patients with newly diagnosed advanced ovarian cancer (OC) modestly improved progression-free survival (PFS), without affecting overall survival (OS).
OC has a poor five-year relative survival rate of 31% in advanced stages. Standard first-line treatment includes debulking surgery and platinum-based chemotherapy (PBCT), with or without bevacizumab, followed by continued bevacizumab maintenance or surveillance. Preclinical studies suggest that combining immune checkpoint inhibitors, like PD-(L)1 inhibitors, with chemotherapy, bevacizumab, or PARP inhibitors may enhance efficacy with a manageable safety profile. The phase III FIRST/ENGOT-OV44 trial (NCT03602859) evaluated the efficacy and safety of adding dostarlimab, a PD-1 inhibitor, to first-line PBCT and niraparib maintenance, with or without bevacizumab, in patients with newly diagnosed advanced OC.1 The primary results were recently published and presented at ASCO 2025.1,2
In this randomised, double-blind, phase III trial, patients with newly diagnosed stage III-IV epithelial OC received 1 cycle run-in of PBCT ± bevacizumab and were randomised (1:1:2) for cycles 2-6 to PBCT with placebo followed by placebo maintenance (arm 1), PBCT with placebo followed by niraparib maintenance (arm 2) or PBCT with dostarlimab followed by dostarlimab-niraparib maintenance (arm 3). Enrolment to arm 1 was terminated early following approval of PARP inhibitors and patients were subsequently randomised (1:2) to arms 2 or 3. Stratification factors included planned use of bevacizumab, homologous recombination repair (HRR) mutation status (BRCA-mutated, BRCA wild type/HRR positive, or HRR negative/unknown), and presence of stage III disease with postoperative residual disease (<1 cm). Efficacy was evaluated in the intention-to-treat population (arms 2 and 3). The primary endpoint was investigator-assessed PFS, and the key secondary endpoint was OS. Safety was assessed in all patient who received at least one dose of study treatment across arms 1-3, analysed according to the treatment received.
A total 1,138 patients were randomised to niraparib (N= 385) and dostarlimab plus niraparib (N=753). After a median follow-up of 53.1 months, PFS was significantly longer in the dostarlimab plus niraparib arm compared to the niraparib arm, with a median PFS of 20.6 vs 19.2 months (HR[95% CI]: 0.85[0.73-0.99], p< 0.035). No significant difference in OS was observed between arms, with 44.4 months for dostarlimab plus niraparib and 45.4 months for niraparib (HR[95% CI]: 1.01[0.86-1.19], p= 0.906). The safety analysis included 1,321 patients and showed results consistent with known safety profiles. The median duration of exposure was 15.2 months in both treatment arms. Treatment-related adverse events (TRAEs) during the chemotherapy period were reported in nearly all patients (92.6% in niraparib and 94.4% in dostarlimab plus niraparib), with grade ≥3 TRAEs occurring in 37.2% and 41.1%, respectively. The most common treatment-emergent AEs of grade ≥3 in the dostarlimab + niraparib arm were anaemia (27.8%) and neutropenia (22.3%). Patient-reported outcomes indicated stable health-related quality of life, functioning, and symptoms, with no clinically significant worsening.
For newly diagnosed patients with advanced OC, the addition of dostarlimab to PBCT and niraparib maintenance resulted in statistically significant, but clinically modest improvement in PFS. No difference in OS was observed. Safety outcomes were consistent with known profiles of the individual agents, and no meaningful differences were seen in patient-reported outcomes.
References
1. Hardy-Bessard AC, Pujade-Lauraine E, Moore RG, et al. Dostarlimab and niraparib in primary advanced ovarian cancer. Ann Oncol 2025; Article in press.
2. 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 ASCO 2025; Abstract LBA5506.
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