Phase II trial of patupilone in patients with brain metastases from breast cancer.

Overview

abstract

BACKGROUND: For patients with progressive breast cancer brain metastasis (BCBM) after whole brain radiotherapy (WBRT), few options exist. Patupilone is an epothilone that crosses the blood-brain barrier. We hypothesized that patupilone would produce a 35% 3-month CNS progression-free survival in women with BCBM after WBRT. METHODS: This multicenter phase II trial included 2 cohorts. Group A included women with progressive BCBM after WBRT. Group B was an exploratory cohort of patients with either leptomeningeal metastases or untreated brain metastases. The primary goal was to observe a 35% 3-month CNS progression-free survival in Group A. The sample size was 45 for Group A and 10 for Group B. Patients received patupilone 10 mg/m(2) once every 3 weeks until progression. Responses were scored according to the Macdonald criteria. RESULTS: Fifty-five patients (45 in Group A, 10 in Group B) enrolled. In Group A, the 3-month CNS progression-free survival was 27%, the median overall survival was 12.7 months, and the overall response rate was 9%. In Group B, which enrolled 5 patients with leptomeningeal disease and 5 with no prior WBRT, no responses occurred and 8 patients had CNS progression before 3 months. Systemic responses occurred in 15% of patients, including a complete response in liver metastases. Diarrhea occurred in 87% of patients; 25% had grade 3 and 4 adverse events. CONCLUSIONS: Patupilone in patients with BCBM did not meet the efficacy criteria and had significant gastrointestinal toxicity. Further study of brain-penetrant agents is warranted for patients with CNS metastases from breast cancer.