Study of lapatinib (T) in combination with trastuzumab (T) in women heavily pretreated with HER2-positive metastatic breast cancer (MBC).

Abstract

e11577 Background: The anti-HER2 monoclonal antibody trastuzumab and the tyrosine kinase inhibitor lapatinib have complementary mechanisms of action and synergistic antitumour activity in models of HER2-overexpressing breast cancer.In heavily pre-treated pts, L+T is associated with improved outcomes compared to L alone and significantly improved progression-free survival (PFS), offering a chemotherapy-free option for patients with heavily pretreated human epidermal growth factor. (Kimberly L et al, 2012 JCO). Methods: We evaluated the safety and efficacy of L+T in patients with 1-4 prior (Median 3) lines of chemotherapy (CT) for HER2+ MBC.: 20 Pts with measurable, HER2+ MBC were eligible. Pts received every 3 weeks T (8 mg/kg loading then 6 mg/Kg) and daily L 1000 mg. Results: The characteristic of the all of pts included (20) are: median age 51.4 (32-68) Total number of cycles administered was 141. The median cycles administered per pts was 6 (range 1-18). Median follow-up was 6 months. Of the 18 pts with response assessment, the clinical benefit obtained was: 76,1% (5,9% PR + and 70,6% disease stabilization) with 95% CI 71.3%-80.9%. Disease progression was 17,6%. Of the 20 pts with a median follow up of 13,32 m (3-32), median PFS for these pts was 6 m. The one year OS % was 64,70% (56,7-72,7). All pts had received al least one line lapatinib prior (1-3). Toxicity was generally manageable. No major cardiac dysfunctions ocurred. Grade 3/4 treatment-related toxicities were uncommon (grade 3 diarrhea, 18%; grade 3 hepatic 7%. All others < 3 %). Conclusions: L+T is an active regimen in HER2+ MBC. L+T showed high clinical benefit with manageable safety profile. Dual inhibition of HER2 might be a valid approach to treatment of Her-2 positive metastatic breast cancer.