Disappointing survival data

PARP Inhibitor Maintenance After First-Line Chemotherapy in Advanced-Stage Epithelial Ovarian Cancer A Systematic Review and Meta-Analysis

https://tinyurl.com/ymznp6pu

For women with ovarian cancer personalised care has been game-changing with expectation of longer and better life. PARP inhibitors help to restore DNA repair pathways and have been shown to significantly lengthen progress free survival (PFS). However, like many medical interventions there is a cost, with increased adverse drug reactions some of which, such as leukaemia, can be fatal.

When assessing randomised clinical trials (RCT) for cancer patients the usual endpoint is the PFS. This is because the duration of such a trial is shorter than a trial which looks at overall survival (OS) which requires a greater time span of 5 years or more. This bias towards shorter trials has resulted in a false confidence that PARP inhibitors may also prolong OS.

This multi-centre study looks at data from 7 RCTs of more than 4000 patients, with advanced ovarian cancer treated with PARP inhibitors as maintenance therapy after initial standard care. No improvement in OS was shown in any of the trials and the risk of significant adverse effects was increased, in one instance being almost 5 times more likely.

The authors suggest that there are differences between outcomes for some of the PARP inhibitor drugs with individual response meaning careful therapy choice is required. Also, use of PARP inhibitors for those 50% of ovarian cancer patients without defective DNA repair is of dubious benefit.