The final overall survival analysis of the phase III PRIMA trial revealed that maintenance niraparib did not significantly improve overall survival (OS) compared to placebo in patients with newly diagnosed advanced ovarian cancer who responded to front-line platinum-based chemotherapy. However, the PARP inhibitor continued to demonstrate a sustained progression-free survival (PFS) benefit, according to findings presented at the European Society for Medical Oncology (ESMO) Congress 2024.
PRIMA Trial Details
The PRIMA trial (ENGOT-OV26/GOG-3012) enrolled 733 patients with advanced high-grade serous or endometrioid ovarian cancer at high risk for recurrence. Participants were randomized 2:1 to receive either niraparib or placebo for up to 3 years following successful platinum-based therapy. The primary endpoint of the trial was progression-free survival.
Overall Survival Results
After a median follow-up of approximately 6 years, the median overall survival was 46.6 months in the niraparib arm and 48.8 months in the placebo arm (hazard ratio [HR] = 1.01; P = .8834). The 5-year overall survival rates were 42% and 44% for niraparib and placebo, respectively.
Progression-Free Survival Benefit
Despite the lack of overall survival benefit, niraparib demonstrated a significant and sustained improvement in progression-free survival. The 5-year progression-free survival rate was 22% with niraparib compared to 12% with placebo (HR = 0.66; 95% confidence interval [CI] = 0.55–0.78).
In the homologous recombination-deficient population, the benefit was even more pronounced. At 5 years, 35% of patients in the niraparib arm were progression-free compared to only 16% in the placebo arm (HR = 0.51; 95% CI = 0.40–0.66).
Time to Next Treatment
Niraparib also prolonged the time to next treatment. In the overall population, the median time to next treatment was 17.0 months with niraparib versus 12.0 months with placebo (HR = 0.74; 95% CI = 0.62–0.89). In the homologous recombination-deficient subset, the median time to next treatment was 26.9 months with niraparib versus 13.9 months with placebo (HR = 0.55; 95% CI = 0.43–0.71).
Impact of Subsequent Therapies
Researchers noted that the absence of an overall survival benefit might be influenced by factors such as extended post-progression survival and the use of subsequent therapies. Notably, a higher percentage of patients in the placebo arm received subsequent PARP inhibitors (37.8% overall, 48.4% in the homologous recombination-deficient subset) compared to the niraparib arm (11.7% overall, 15.8% in the homologous recombination-deficient subset).
Antonio González-Martín, MD, PhD, of the Cancer Center Clínica Universidad de Navarra, suggested that overall survival analyses adjusted for second-line PARP inhibitor use indicate that subsequent treatments may have had an impact on the final results.
Safety Profile
With up to 7 years of follow-up, no new safety signals were observed. The incidence of myelodysplastic syndrome and acute myeloid leukemia was 2.3% with niraparib and 1.6% with placebo.
Expert Commentary
Philipp Harter, MD, PhD, of the Evang Kliniken Essen-Mitte, commented that while the lack of overall survival benefit is disappointing, the sustained progression-free survival benefit confirms that niraparib remains a standard option as maintenance therapy in patients with advanced ovarian cancer. He also noted that the safety profile of PARP inhibitors in this setting is reassuring.
Dr. Harter suggested that future trials should focus on optimizing the duration of PARP inhibitor maintenance therapy, potentially limiting it to 2 years or less, to balance benefits and risks.
