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Update on PARP Inhibitors

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by Lisa Schlager

Dr. Judy Garber of Dana-Farber Cancer Institute discussed recent PARP inhibitor (PARPi) research. Six different PARPis are being studied in three dozen clinical trials. Results on two PARPis, olaparib and iniparib, were presented at ASCO.

Despite early enthusiasm, the recent phase III trial for triple-negative breast cancer — cancer that does not express estrogen or progesterone receptors or the protein Her2neu — using iniparib did not demonstrate enough survival benefit to receive FDA approval. Promising early PARPi research focused on people with BRCA mutations, while the phase III trial was open to women with advanced breast cancer, regardless of BRCA status. Although women with BRCA1 mutations tend to get triplenegative breast cancer, not all triplenegative tumors behave alike. Yet BRCA testing was not conducted on study participants so we don't know if mutation carriers responded best to the therapy. There is also speculation that iniparib may work differently than other PARPis, and that another mechanism may be responsible for its effects. More research is needed to determine target patients and gain FDA approval for iniparib.

AstraZeneca's phase II olaparib trial improved progression-free survival by four months in women with a common type of ovarian cancer relapse. This is the first randomized trial using a PARPi in ovarian cancer. It is also the first ovarian cancer randomized trial to demonstrate benefit from maintenance therapy (therapy given over an extended period of time to prevent recurrence). Larger trials are needed to validate these results.

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