A randomized and open-label trial evaluating the addition of pazopanib to lapatinib as first-line therapy in patients with HER2-positive advanced breast cancer.

摘要

This phase II study (VEG20007; NCT00347919) with randomized and open-label components evaluated first-line lapatinib plus pazopanib therapy and/or lapatinib monotherapy in patients with human epidermal growth factor receptor type 2 (HER2)-positive advanced/metastatic breast cancer. Patients were enrolled sequentially into two cohorts: Cohort 1, patients were randomly assigned to lapatinib 1,000?mg plus pazopanib 400?mg or lapatinib 1,500?mg monotherapy; Cohort 2, patients received lapatinib 1,500?mg plus pazopanib 800?mg. The primary endpoint was week-12 progressive disease rate (PDR) for Cohort 1. The principal secondary endpoint was week-12 response rate (RR) for Cohort 2. Efficacy was assessed in patients with centrally confirmed HER2 positivity (modified intent-to-treat population [MITT]). The study enrolled 190 patients (Cohort 1, combination n?=?77, lapatinib n?=?73; Cohort 2, n?=?40). The MITT population comprised n?=?141 (Cohort 1) and n?=?36 (Cohort 2). In Cohort 1, week-12 PDRs were 36.2?% (combination) versus 38.9?% (lapatinib; P?=?0.37 for the difference). Week-12 RRs were 36.2?% (combination) versus 22.2?% (lapatinib). In Cohort 2, week-12 RR was 33.3?%. In Cohort 1, grade 3/4 adverse events (AEs) included diarrhea (combination, 9?%; lapatinib, 5?%) and hypertension (combination, 5?%; lapatinib, 0?%). Grades 3/4 AEs in Cohort 2 included diarrhea (40?%), hypertension (5?%), and fatigue (5?%). Alanine aminotransferase elevations?>5 times the upper limit of normal occurred in Cohort 1 (combination, 18?%; lapatinib, 5?%) and Cohort 2 (20?%). Upon conclusion, the combination of lapatinib plus pazopanib did not improve PDR compared with lapatinib monotherapy, although RR was increased. Toxicity was higher with the combination, including increased diarrhea and liver enzyme elevations.