Cisplatin chemotherapy in the treatment of BRCA1-positive metastatic breast cancer (MBC)

Abstract

1099 Background: Preclinical data suggest that women with BRCA1 related breast cancers may be particularly sensitive to chemotherapeutic agents that cause DNA damage such as cisplatin chemotherapy. This study was conducted to assess the efficacy and safety of cisplatin chemotherapy in patients with BRCA1 positive MBC. Methods: This was a multicenter, open label, single arm study of cisplatin 75 mg/m2 given intravenously every three weeks until disease progression or toxicity. The primary objective was to assess antitumour activity of cisplatin, as measured by clinical benefit response (CR, PR, or SD ≥ 6 months). Eligible patients had locally recurrent or MBC, had 0–2 prior chemotherapy regimens in the metastatic setting, and had received prior therapy with an anthracycline. Patients were restaged every eight weeks. The study protocol was approved by the institutional review boards of participating institutions. Results: A total of 15 patients were enrolled. Mean age was 48.1 years (range: 32 to 70). ECOG performance status scores were 0 (6 pts), 1 (5 pts), 2 (4 pts). All patients had a confirmed BRCA1 mutation (7 with C61G mutation, 7 with 5382 insC, 1 with 4153delA). Five patients (33%) were ER or PR + and none were HER-2+. Prior history of MBC chemotherapy included 1 regimen (4 pts) and 2 regimens (7 pts). Seven (46%) and 4 (26%) patients had complete and partial responses by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, for an overall response rate of 72%. Median duration of response has not yet been reached. In general, cisplatin was well tolerated. Neutropenia was the commonest toxicity with 33% grade 2 (6,7% and 0%, grades 3 and 4 neutropenia). No patients developed febrile neutropenia. Conclusions: Significant activity and favorable toxicity profile provides a basis for considering cisplatin for further evaluation in phase III trials for women with BRCA1 positive MBC. No significant financial relationships to disclose.