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Data Confirm PARP Inhibitor Slows Ovarian Ca (CME/CE)
MedPageToday, 2012However, most patients relapse, and responses to subsequent therapies tend to be of shorter duration compared with the initial response.
About 15% of epithelial ovarian cancers have homologous repair deficiency arising from BRCA1/2 mutations.
As many as 50% of high-grade serous ovarian tumors are deficient in the homologous repair enzyme as a result of germline or acquired BRCA1/2 mutations or defects in the homologous repair pathway, according to the introduction of the journal article.
Silencing or abnormal function of genes in BRCA1/2 -related pathways has given rise to a so-called "BRCAness" phenotype, a term referencing the similarity to inherent mutations in BRCA1/2 .
Microarray analysis of serous ovarian tumors has revealed a BRCAness gene-expression profile that appears to predict responsiveness to platinum chemotherapy and inhibitors of poly(adenosine diphosphate [ADP]-ribose) polymerase, or PARP, authors of the journal article continued.
A phase II study of of patients with high-grade serous ovarian cancer, single-agent olaparib resulted in a response rate 41% in patients with BRCA1/2 mutations and 24% in those without mutations.
The favorable clinical and preclinical data provided the basis for a randomized trial of olaparib maintenance therapy in patients with relapsed, platinum-sensitive, high-grade serous ovarian cancer.
Eligibility criteria included a history of at least two courses of platinum-based chemotherapy, the most recent of which had resulted in an objective response.
Additionally, pretreatment measurements of the CA-125 cancer antigen had to be within the upper limit of normal.
Within 8 weeks after the last dose of platinum-based chemotherapy, investigators randomized 264 patients to daily olaparib or placebo and followed them until disease progression, death, or discontinuation.
At the planned interim analysis, the results showed a significant improvement in PFS in the olaparib arm (HR 0.35, P <0.001).