As a new feature of OncoFacts, we will be highlighting some of the most interesting and potentially practice-changing clinical trials for different malignancies. Because of my particular interest in breast cancer, I have chosen to highlight these clinical trials first. I will begin by highlighting some trials for early breast cancer, and then will review a trial for advanced breast cancer.

Therapy for Metastatic Breast Cancer

A phase III, multi-center study of gemcitabine/carboplatin, with or without BSI-201, in patients with ER-, PR-, and HER2-negative metastatic breast cancer

Why is this trial being done? Poly (ADP-ribose) polymerase (PARP) is a key regulator of DNA damage repair and is involved in DNA base-excision repair. PARP binds directly to DNA damage and produces large branched chains of poly (ADP-ribose) in order to repair the single-chain breaks. Some chemotherapy drugs (especially the platins) inflict DNA damage via adducts and DNA cross-linking. When this occurs, PARP1 is upregulated and repairs the damage of to the DNA. PARP inhibitors inhibit PARP1 and disable DNA base-excision repair, leading to cell death. The decision to commence with the phase III study was made based on phase II study results presented during the Plenary Session of the American Society of Clinical Oncology^® (ASCO) annual conference on May 31, 2009. The phase II clinical trial involved 116 women with metastatic triple-negative breast cancer who were randomly assigned to receive gemcitabine-carboplatin in combination with the investigational agent BSI-201 or gemcitabine-carboplatin alone.

Approximately 62% of patients receiving BSI-201 in combination with gemcitabine-carboplatin showed clinical benefit, compared with 21% in the group receiving chemotherapy alone (P = .0002). Tumor response (complete or partial response) was observed in 48% of patients who received BSI-201 combined with chemotherapy, whereas patients receiving chemotherapy alone showed a response rate of 16%. Women who received BSI-201 had a median PFS of 6.9 months and OS of 9.2 months compared with 3.3 and 5.7 months, respectively, for women who received chemotherapy alone. The hazard ratios for PFS and OS were 0.342 (P<.0001) and 0.348 (P = .0005), respectively

Who is eligible? Women with metastatic, measurable breast cancer that is triple-negative (ER-negative, PR-negative, and HER2 non-amplified) are eligible. Women will be stratified into 2 groups: those who have never received chemotherapy for metastatic disease, or those who have received 1 or 2 prior chemotherapy regimens in the metastatic setting.

Study Schema: Women will be randomly assigned to 1 of 2 treatment arms:

1. Gemcitabine 1000 mg/m² IV days 1 and 8 and carboplatin AUC 2, IV days 1 and 8 on an every 21 day cycle
2. Gemcitabine-carboplatin as above with BSI-210 5.6 mg/kg IV d 1, 4, 8, 11 on an every 21 day cycle.

Statistical Outcomes: This trial will randomize 420 triple-negative metastatic breast cancer patients. The co-primary objectives of this study are to assess improvement in PFS and OS. The secondary objectives are to assess objective response rate and safety. An estimated 60 to 75 sites will be distributed throughout the United States. Importantly, this trial will have a crossover provision that will ensure that all patients enrolled in the BSI-201 phase III clinical trial have the potential opportunity to receive BSI-201 (patients randomly assigned to the control arm may receive BSI-201 upon disease progression).

ClinicalTrials.gov. Available from: http://clinicaltrials.gov/ct2/show/NCT00938652?term=BiPar&rank=1. Accessed September 4, 2009.

OncoFacts™ Editor:

Christy Russell, MD

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