Phase III Trial Fails to Find Benefit of PARP Inhibitor for TNBC

by Dr. C.H. Weaver M.D. 8/1/2016

In a Phase III clinical trial, the addition of the PARP inhibitor iniparib to chemotherapy did not improve outcomes among women with metastatic triple-negative breast cancer. These results—which differ from those of a prior Phase II clinical trial—were presented at the 2011 annual meeting of the American Society of Clinical Oncology.

Breast cancers that are estrogen receptor-negative, progesterone receptor-negative, and HER2-negative are called triple-negative breast cancers. Triple-negative breast cancers tend to be more aggressive than other breast cancers and have fewer treatment options.

Iniparib belongs to a class of drugs called PARP inhibitors. The PARP enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Drugs that inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy. Because many triple-negative breast cancers are thought to have defects in DNA repair, researchers have hypothesized that triple-negative breast cancers may be particularly vulnerable to PARP inhibition.

A Phase II clinical trial provided hope that iniparib would indeed provide a valuable new treatment option for triple-negative breast cancer. Results published in the New England Journal of Medicine early in 2011 suggested that the addition of iniparib to chemotherapy with Gemzar® (gemcitabine) and carboplatin delayed cancer progression and improved overall survival.[1] Median overall survival was 7.7 months among women treated with chemotherapy alone and 12.3 months among women treated with chemotherapy plus iniparib.

A subsequent Phase III clinical trial, however, did not find a benefit. The study enrolled a larger group of women (519 versus 123 in the Phase II trial), and once again compared chemotherapy alone with chemotherapy plus iniparib for the treatment of metastatic triple-negative breast cancer. According to results presented at the 2011 annual meeting of the American Society of Clinical Oncology, the addition of iniparib did not significantly improve overall or progression-free survival.[2]

Although the Phase III results were a great disappointment, it remains possible that iniparib could still provide a benefit to women whose cancer has progressed (worsened) on other treatments. Researchers are continuing to explore whether there are particular subsets of women who respond well to this treatment.


[1] O’Shaughnessy J, Osborne C, Pippen JE et al. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. New EnglandJournal of Medicine. 2011;364:205-214.

[2] O’Shaughnessy J, Schwartzberg LS, Danso MA et al. A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC). Presented at the 2011 annual meeting of the American Society of Clinical Oncology. Chicago, IL. June 3-7, 2011. Abstract 1007.

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