Cell Therapeutics, Inc. (CTI) has announced the interim results from a cooperative group sponsored phase II clinical trial of brostallicin in combination with cisplatin for the treatment of women with metastatic triple-negative breast cancer. These results were presented from December 4-8, 2012 at the San Antonio Breast Cancer Symposium (SABCS).

The study enrolled women with confirmed measurable metastatic disease and triple negative subtype breast cancer. At the time of data analysis, 48 women had been enrolled in the study and 47 were evaluable for efficacy. Approximately half of the patients had received between two and four prior chemotherapy regimens in the metastatic setting. The primary endpoint of the trial is three-month progression-free survival (PFS). Secondary endpoints include overall response rate (ORR), duration of response, six-month PFS, overall survival (OS) and safety. In this study, patients received cisplatin on Day 1, brostallicin on Day 2, and GCSF or pegylated-GCSF on Day 3, with the cycle repeated every 21 days.

The study is led by principal investigator Dr Alvaro Moreno-Aspitia, assistant professor of Medicine, Mayo Clinic, Jacksonville, FL. Key findings include:

As of this analysis, 10 of 47 evaluable patients (21%) achieved a confirmed tumor response. Nine patients had a partial response (PR) and one confirmed response (CR).

Despite the heavily pretreated population, three-month PFS was at 51 per cent and six-month PFS is currently 26 per cent.

Median duration of response was 3.4 months; median time to progression was 3.2 months.

Adverse events were mostly haematologic (74.5 per cent) and consistent with other treatments in this setting.

Triple-negative breast cancer lacks progesterone and estrogen receptors and the HER2 biomarker that is present in most breast cancers, which makes standard therapy with hormone or targeted therapy ineffective. The authors concluded that in this study the combination of brostallicin and cisplatin showed promising activity in heavily pretreated metastatic triple-negative breast cancer patients and achieved its primary endpoint comparing favorably to other phase II clinical trials in this disease. Final results of this trial are expected to be presented at the American Society of Clinical Oncology 2013 Annual Meeting. A follow-up randomized phase II trial is in development.

Triple-negative breast cancer whose cells lack estrogen receptors and progesterone receptors, and do not have an excess of the HER2 protein on their surfaces. Breast cancers with these characteristics tend to occur more often in younger women and in African-American women. Triple-negative breast cancers tend to grow and spread more quickly than most other types of breast cancer. Because the tumor cells lack these certain receptors, neither hormone therapy nor drugs that target HER2 are effective treatments (but chemotherapy can still be useful if needed). About 10 per cent to 20 per cent of breast cancers are triple negative.

Brostallicin, a novel synthetic second-generation DNA minor groove binder, has shown potent cancer killing activity, and has demonstrated synergism in combination with standard cytotoxic agents as well as with newer targeted therapies, in preclinical experimental tumour models. Brostallicin binds covalently to DNA within the DNA minor groove, interfering with DNA division and leading to tumor cell death.

Cell Therapeutics is a biopharmaceutical company committed to the development and commercialisation of an integrated portfolio of oncology products aimed at making cancer more treatable.