Phase I trial of panobinostat (LBH589) in combination with trastuzumab in pretreated HER2-positive metastatic breast cancer (mBC): Preliminary safety and tolerability results

1081 Background: Panobinostat is a potent inhibitor of histone deacetylase (HDAC) and has demonstrated single-agent activity and synergistic effects in combination with trastuzumab or docetaxel in HER2 positive BC xenografts. Methods: Previously treated mBC patients (pts), who progressed on or within 6 months of trastuzumab-based therapy, were enrolled in this multicenter study. Pts were dosed with either i.v. (Day 1+8) or oral panobinostat (three times per week, continuously) every three weeks in combination with standard weekly dose trastuzumab. To establish maximum tolerated dose, three (10, 15, and 20 mg/m2) and four (15, 20, 30 and 40 mg) cohorts are planned for treatment with i.v. and oral panobinostat, respectively. The pharmacokinetic (PK) profile is also measured. Results: Eighteen pts have been enrolled in this ongoing trial. Median age 54 yrs (33–60). Six pts were ER and PR negative, eight pts had liver metastasis, eight pts had lung metastasis, and two pts had central nervous system metastasis...