PARPi in Advanced Ovarian Cancer; Does it Prolong Survival?
Ashley McMurray, Chantelle Burl, Dr Kate Levett, Dr Ekavi Georgousopoulou
Background :
Ovarian cancer is the sixth leading cause of cancer-related mortality and the second most lethal gynaecological cancer affecting Australian women. Poor prognosis for advanced ovarian cancer necessitated development of novel drug therapies such as Poly-ADP Ribose Polymerase inhibitors (PARPi) for maintenance therapy. Given recent introduction of PARPi and the publication of new research it is important to summarise the available clinical trial data to provide evidence-based guidance for clinicians.
Objectives:
In this meta-analysis we aimed to evaluate PARPi maintenance therapy on progression free survival (PFS) and overall survival (OS) of BRCA-mutated (BRCAm) advanced ovarian cancer. We examined Olaparib and Niraparib as they are the only PARPi accessible through the Australian PBS.
Method:
A systematic review and meta-analysis were performed on phase II and III trials assessing the efficacy of Olaparib or Niraparib maintenance therapy on BRCAm advanced ovarian cancer. Two databases were searched, and bias was assessed using the Cochrane risk-of-bias tool for randomized trials (RoB2). For the meta-analysis, a random effects model was used.
Results:
Ten studies were included in the meta-analysis, reporting on six clinical trials and 1373 participants. The use of Olaparib compared to placebo provides a clinically significant OS benefit, with a pooled Hazard Ratio (HR) of 0.63 (95% CI = [0.51-0.76], p=<0.001). Niraparib did not provide a statistically significant OS benefit (HR = 0.89 [0.68-1.15] p=0.36). Additionally, Niraparib and Olaparib maintenance therapy provided significant PFS benefits (pooled Niraparib HR = 0.37 [0.27-0.51], p<0.001) (Pooled Olaparib HR = 0.32 [0.26-0.39], p<0.001).
Conclusions:
The use of Niraparib and Olaparib as maintenance therapy in BRCAm advanced ovarian cancer patients provides statistically significant improvements to PFS. In this meta-analysis neither were shown to be definitively superior. In this population, the use of Olaparib also generates an improvement in OS. This is not replicated with the use of Niraparib.