Journal of the European Society for Gynaecological Endoscopy

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New perspective on maintenance therapies for platinum- sensitive recurrent ovarian cancer in women with germline and somatic mutations in BRCA1 and BRCA2 genes 

I. Vergote1, V. Bours 2, B. BlaumeIser 3, J-F. BauraIn 4

1 Division of Gynecological Oncology, Leuven Cancer Institute, and Department of Gynaecology and Obstetrics, KU Leuven, 3000 Leuven, Belgium.
2 Human Genetics Unit, GIGA-Cancer Research, University of Liège, and Genetics Center, CHU Liège, 4000 Liège, Belgium.
3 Department of Medical Genetics, Antwerp University and University Hospital UZA, 2650 Edegem, Belgium
4 The King Albert II Cancer Institute, Cliniques universitaires Saint-Luc, Université catholique de Louvain, 1200 Bruxelles, Belgiumi 

Keywords:

BRCA 1, BRCA 2, cancer, maintenance therapy, platinum-sensitive recurrent ovarian cancer. 


Published online: Dec 08 2016

Abstract

Ovarian cancer (OC) is the seventh most common cancer in women. Although women diagnosed with OC are usually treated frontline with platinum-based chemotherapy, most of them relapse once treatment is halted. Therefore, maintenance therapies have been developed to secure the response and delay further chemotherapy. There are two established maintenance therapies for women affected by platinum-sensitive recurrent OC: bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growth factor, and olaparib, an inhibitor of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARPi). Loss-of-function mutations in genes in the homologous recombination pathway, especially BRCA1 and BRCA2, predict higher rates of platinum sensitivity, better overall survival (OS), and better response to PARPi in women with OC. Among patients with platinum-sensitive recurrent OC, a BRCA mutation is the rst genetically de ned predictive marker for targeted therapy, since these patients are most likely to bene t from treatment with a PARPi, such as olaparib. In patients with platinum-sensitive recurrent OC without a BRCA mutation, bevacizumab currently seems to be the best maintenance option. Women with OC are progressively more routinely screened for germline BRCA mutations, and the implication of somatic BRCA mutations is increasingly being recognized in OC. Therefore, the recommendations should be updated to reflect the importance of both types of mutations. Together, these data highlight the fact that treatment of recurrent OC can be optimized using genomic contributions to individualize therapy and to improve treatment response.