Long-Term Effects of PARP Inhibitors in HRD-Positive Ovarian Cancer

By: Jenna Carter, PhD
Posted: Tuesday, January 21, 2025

The use of PARP inhibitors as a maintenance treatment following first-line chemotherapy has shown potential in patients with BRCA-mutated and homologous recombination–deficiency (HRD)-positive ovarian cancer yet also has raised some concerns. To shed light on the matter, Eleonora Ghisoni, PhD, of the University Hospital of Lausanne, Switzerland, and colleagues investigated the newly available evidence concerning unfavorable outcomes. Their findings, which were published in ESMO Open, emphasize the importance of long-term follow-up and real-world data to further define whether and when it is safe to stop PARP inhibitors.

Survival data for PARP inhibitors were observed for late lines of treatment in the SOLO-3 and ARIEL-4 trials. Data from the NOVA, SOLO1, PAOLA-1, ARIEL-3, PRIMA, and ATHENA-mono phase III trials were also included in this investigation. The primary endpoint of these studies was progression-free survival and not overall survival, so the study authors noted their final conclusions should be interpreted with caution.

Long-term data on overall survival revealed no detrimental effects with PARP inhibitor for patients with BRCA mutations in both the SOLO-3 and ARIEL-4 trials; however, there was no advantage seen (niraparib: hazard ratio [HR] = 0.85, 95% confidence interval [CI] = 0.61–1.2; rucaparib: HR = 0.86, 95% CI = 0.99–1.7). Overall survival data for niraparib and rucaparib in patients with wild-type BRCA mutations in the NOVA and ARIEL-3 trials suggested a survival decrement in patients without germline BRCA mutation, whereas the median overall survival in the NOVA trial was 31.1 months with niraparib and 36.5 months in the placebo arm (HR = 1.10, 95% CI = 0.831–1.459). In the ARIEL-3 trial, survival with rucaparib was not improved in the experimental arm, with a median of 36.0 months with rucaparib and 43.2 months with placebo (HR = 0.995, 95% CI = 0.809–1.223). Toxicity findings established that patients were at increased risk of developing myelodysplastic syndrome and acute myeloid leukemia, and further research is necessary to gauge the optimal treatment duration.

Disclosure: Dr. Ghisoni reported no conflicts of interest. For full disclosures of the other study authors, visit www.esmoopen.com.

ESMO Open