PARP Inhibitors and the Evolving Landscape of Ovarian Cancer Management: A Review

AbstractAs a drug class, inhibitors of poly-(ADP-ribose) polymerase (PARP) have had their greatest impact on the treatment of women with epithelial ovarian cancers (EOC), in particular, those with the most common histological subtype, high-grade serous cancer, as it has high rates of homologous recombination (HR) deficiency. PARP inhibition exploits this cancer vulnerability by further disrupting DNA repair, thus leading to genomic catastrophe. Early clinical data demonstrated the effectiveness of PARP inhibition in women with recurrent EOC harbouringBRCA1/2 mutations and those with platinum-sensitive recurrences. Three PARP inhibitors (olaparib, niraparib, and rucaparib) are now approved for use in women with recurrent EOC. Based upon randomised controlled trials, PARP inhibitors are in use as “maintenance” therapy for those with platinum-sensitive and platinum-responsive recurrences (irrespective ofBRCA1/2 mutation status). Among women withBRCA1/2 mutations (either germline or somatic), maintenance PARP inhibitor therapy for those with recurrence has led to a nearly fourfold prolongation of progression-free survival compared to placebo control. Those withoutBRCA1/2 mutations experience an approximately twofold increase in progression-free survival. The latest clinical data demonstrate that women withBRCA1/2 mutations who respond to first-line chemotherapy and go on to have maintenance olaparib experience a doubling of the rate of freedom from death at 3  years when com...

Source: BioDrugs - March 20, 2019 Category: Drugs & Pharmacology Source Type: research