Niraparib for the treatment of ovarian cancer.

Expert Opin Pharmacother

a Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre , University of Toronto, Toronto , Canada.

Published: April 2017

Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors are being developed in maintenance and recurrence treatment settings in ovarian cancer. They inhibit single-stranded DNA repair, inducing synthetic lethality in cells with underlying homologous recombination deficiency (HRD). Marked responses are seen in ovarian cancers with breast cancer gene 1 (BRCA1) or 2 (BRCA2) mutation, although up to 50% of high-grade serous ovarian cancers (HGSOC) have HRD may also benefit. Areas covered: This review focuses on niraparib (oral PARP I and II inhibitor), its clinical testing in ovarian cancer, including the Myriad MyChoice HRD test as a potential companion diagnostic. Future directions plus ongoing trials, including novel combinations are highlighted. Expert opinion: There is now level 1 evidence of efficacy from the first randomized placebo-controlled phase III trial using niraparib maintenance in women with platinum-sensitive recurrent HGSOC with complete or partial response post platinum-based chemotherapy. Niraparib improved progression free survival over placebo in all groups of women. The benefit was greatest in patients with germline BRCA1/2 mutation, followed by HRD positive tumors; however, absence of either does not exclude the possibility of benefit from niraparib maintenance. Additional studies are underway with niraparib in the first line maintenance, and 4/5 line recurrence treatment settings.

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Source
http://dx.doi.org/10.1080/14656566.2017.1297423DOI Listing

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