Olaparib for the treatment of relapsed ovarian cancer with a BRCA1/2 mutation.

INTRODUCTION: Despite treatment strategies which include both surgery and chemotherapy, epithelial ovarian cancer often relapses and survival rates remain poor. There is therefore a need to identify novel treatment targets and develop approaches that improve outcomes. The role of both germ line and somatic mutations in BRCA1 and BRCA2 in the development of ovarian cancer is well established, with mutation in either gene resulting in deficiencies in homologous recombination. Olaparib is an orally active inhibitor of poly(ADP-ribose) polymerase (PARP) which has demonstrated anti-tumor activity in ovarian cancer. Areas covered: This review focuses on the rationale for olaparib therapy in the context of relapsed epithelial ovarian cancer associated with a BRCA1 or BRCA2 mutation and summarizes the existing efficacy and safety data in this context. Ongoing phase III trials will be discussed. Expert commentary: Research regarding the optimal use of olaparib in the context of relapsed epithelial ovarian cancer associated with a BRCA mutation continues, with evidence for its use as maintenance therapy, treatment as a single agent and in combination with other targeted agents. The mechanisms of resistance require further exploration and it remains to be established whether retreatment or combination with other agents are viable treatment strategies.