Poly(ADP-ribose) polymerase (PARP) inhibitors have emerged as a promising therapeutic strategy in the management of epithelial ovarian cancer (EOC), particularly as maintenance therapy following chemotherapy. A comprehensive review of 15 studies involving 6109 participants, highlights the benefits and risks associated with PARP inhibitor use in both newly-diagnosed and recurrent EOC. The analysis, incorporating data from various PARP inhibitors such as olaparib, niraparib, and rucaparib, reveals significant improvements in progression-free survival (PFS) but a less clear impact on overall survival (OS).
Efficacy in Newly-Diagnosed and Recurrent EOC
The review indicates that PARP inhibitor maintenance treatment after chemotherapy may improve PFS in women with newly-diagnosed and recurrent platinum-sensitive EOC. Specifically, in recurrent platinum-sensitive EOC, PARP inhibitor maintenance therapy resulted in a large PFS benefit (HR 0.34, 95% CI 0.28 to 0.42). However, the effect on OS was less pronounced, with data still considered immature. In newly diagnosed EOC, PARP inhibitors probably results in little to no difference in OS (two studies, 1124 participants; HR 0.81, 95%CI 0.59 to 1.13).
Impact on Quality of Life and Adverse Events
While PARP inhibitors demonstrate efficacy in prolonging PFS, their use is associated with an increased risk of serious adverse events (grade 3 or higher). These include hematological toxicities, such as anemia and thrombocytopenia, as well as gastrointestinal side effects like nausea and vomiting. Fatigue is also a significant concern, with one meta-analysis finding that PARP inhibitors increase the risk of both all-grade and high-grade fatigue (RR 1.25, 95%CI 1.20 to 1.31). The increased risk of severe adverse events may have a significant impact on quality of life. Quality of life data were generally poorly reported in the included studies.
Role in Platinum-Resistant Disease
The role of PARP inhibitors in platinum-resistant EOC remains less clear, with limited data available. Two studies comparing PARP inhibitors with chemotherapy in this setting showed very low certainty of evidence, highlighting the need for further research to determine the potential benefits and risks in this specific patient population.
Considerations for Clinical Practice
The review underscores the importance of considering both the benefits and risks of PARP inhibitors in the management of EOC. While these agents can significantly improve PFS, particularly in patients with BRCA mutations or homologous recombination deficiencies (HRD), clinicians must carefully weigh these benefits against the potential for increased adverse events and their impact on quality of life. Evidence is most robust for olaparib, with less complete data for veliparib, niraparib and rucaparib.
Further research is needed to identify specific subgroups of patients who are most likely to benefit from PARP inhibitor therapy, as well as to optimize dosing regimens and manage adverse events effectively. Additionally, long-term follow-up data are needed to fully assess the impact of PARP inhibitors on overall survival and to determine whether these agents truly delay the onset of recurrent disease or provide a more durable benefit.
