[PARP INHIBITORS FOR ADJUVANT TREATMENT FOR OVARIAN CANCER]

Treatment for ovarian cancer has been challenging for many years. It is composed of debulking surgery and chemotherapy. During the first line of treatment most patients are sensitive to primary platinum-based chemotherapy, however, unfortunately, most of them will suffer from recurrence in 36 months. About 20-25% of ovarian cancer patients exhibit a germ line mutation in the pathway of double strand DNA repair including BRCA. Poly ADP ribose polymerase inhibitors (PARP Inhibitors) may inhibit enzymes responsible for single strand DNA repair, thus leaving the BRCA mutated cell without a repair mechanism for DNA damage leading to synthetic lethality. Recently, phase 3 studies have shown that ovarian cancer patients with recurrent, platinum sensitive disease who were treated with PARP inhibitors have shown statistically significant improvement in progression free survival. A recent pivotal trial has shown the addition of PARP inhibitor, as a maintenance treatment after first line chemotherapy to ovarian cancer patients with BRCA mutation, had significantly increased the progression-free survival. The side effect profile of PARP inhibitors was tolerable and manageable, although they should be well familiar to care givers. Following these studies, the FDA and the European authorities granted an accelerated approval for the use of PARP inhibitors as maintenance treatment after first line treatment, for BRCA carriers, and at the recurrence for platinum sensitive patients. Subsequently, it was added to the benchmark medications for recurrent platinum sensitive BRCA carriers (germ line or somatic) by the Ministry of Health in Israel. The future seams to provide new combination treatments of PARP inhibitors with immunological agents and vascular endothelial growth factors inhibitors aiming to improve the poor prognosis of ovarian cancer patients.