Results from a randomized Phase III trial evaluating iniparip (BSI-201) in patients with metastatic triple-negative breast cancer (mTNBC) show that the trial did not meet the pre-specified criteria for significance for co-primary endpoints of overall survival and progression-free survival.

When women are diagnosed with breast cancer, their tumors are routinely tested for the presence of estrogen and progesterone receptors and for the over-expression of HER2. However, 15 to 20% of all breast cancers lack over-expression of all three proteins ? giving rise to the term ‘triple-negative breast cancer’ or TNBC. Research has shown TNBC continues to be difficult to treat and associated with poorer outcomes than other types of breast cancer. Women with TNBC are not candidates for hormonal therapies such as tamoxifen or therapies targeting the human epidermal growth factor receptor 2, such as trastuzumab (Herceptin, Roche/Genentech) leaving chemotherapy as the standard treatment. Therefore, finding new strategies to enhance the effectiveness of chemotherapy in this population has become an important research focus.

A New Focus
Iniparib (BSI-201) is a novel investigational anti-tumor agent with poly (ADP-ribose) polymerase (PARP) inhibitory activity in preclinical models. Iniparib (BSI-201) is in Phase III trials for patients with squamous non-small cell lung cancer, as well as in Phase II trials for patients with breast, lung and other cancers. The drug is being developed by BiPar Pharmaceuticals is a subsidiary of Sanofi-Aventis , located in South San Francisco, California.

The study enrolled 519 women with mTNBC from 109 sites in the United States. Patients were randomized to receive a standard chemotherapy regimen (gemcitabine and carboplatin) on days one and eight of each 21-day cycle, with or without iniparib (BSI-201) 5.6 mg/kg, which was administered on days one, four, eight and 11 of each 21-day cycle. Patients in the study had received up to two previous lines of chemotherapy in a metastatic setting. The co-primary endpoints were overall survival and progression-free survival.

The results of a pre-specified analysis in patients treated in the second- and third-line setting demonstrate an improvement in overall survival and progression-free survival, consistent with what was seen in the Phase II study. The overall safety analysis indicates that the addition of iniparib (BSI-201) did not significantly add to the toxicity profile of gemcitabine and carboplatin.

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“While this trial did not meet its primary goal, we believe that the improvement in overall survival and progression-free survival in patients in the second- and third-line setting are important findings,” said Dr. Debasish Roychowdhury, Senior Vice President and Head of Sanofi-Aventis Oncology. “We are conducting in-depth analysis to gain further insight into these Phase III results. Sanofi-aventis remains committed to improving outcomes for patients with triple-negative breast cancer where there is high unmet medical need.”

Sanofi-Aventis plans to discuss these data with United States and European health authorities in the near future. Full study results will be presented at an upcoming major oncology conference. Patients with questions are encouraged to consult with their treating physicians, or call 1-800-633-1610. The current clinical development program for iniparib (BSI-201) continues in breast, lung and other cancers.

For more information:
FDA Grants BSI-201 Fast Track Designation for Metastatic Triple-Negative Breast Cancer.
Iniparib (BSI-201) Extends Overall Survival in Metastatic Triple-Negative Breast Cancer (mTNBC).
Positive Phase II Results with Iniparib (BSI-201) in Women with Metastatic Triple Negative Breast Cancer

[1] O?Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, Chou Koo I, Sherman BM, Bradley C. Iniparib plus Chemotherapy in Metastatic Triple-Negative Breast Cancer
[2] O’Shaughnessy J Osborne C. Pippen JE,. Yoffe M, Patt D, Monaghan G, Rocha C, Sherman B.M, Bradley C. Final efficacy and safety results of a randomized phase II study of the parp inhibitor iniparib (BSI-201) in combination with gamcitabine/carboplatin in metastatic triple negative breast cancer” ESMO 2010; Abstract LBA11.
[3] Loibl S, Mueller B, Von Minckwitz G, Blohmer JU, d. Bois A, et al. PARP expression in early breast cancer and its predictive value for response to neoadjuvant chemotherapy.J Clin Oncol 28:15s, 2010 (suppl; abstr 10511)
[4] Goswami J, Goyal S, Wu H, Moran MS, Haffty BG, et al. Poly(ADP-ribose) polymerase-1 (PARP-1) expression in patients treated with breast-conserving surgery and radiation therapy (BCS+RT). J Clin Oncol 28:15s, 2010 (suppl; abstr 582)

Clinical Trial Information:
Clinical Trial: NCT00540358. A Phase 2 Trial of Standard Chemotherapy, With or Without BSI-201, in Patients With Triple Negative Metastatic Breast Cancer

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