A7: Lapatinib With Capecitabine in Heavily-pretreated HER2- positive Metastatic Breast Cancer Progressing On Trastuzumabce
1centre anti cancer, Blida, Algeria
Lapatinib is an oral small-molecule tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 (HER2) and epidermal growth factor receptor (EGFR); this mechanism of action is distinct from that of Trastuzumab. Lapatinib is active in combination with Capecitabine in women with HER2-positive metastatic breast cancer (MBC) that has progressed after Trastuzumab-based therapy. We evaluated the use of Lapatinib plus Capecitabine in patients with HER2-positive MBC who progressed on Trastuzumab.
Between October 2009 and May 2013, 42 patients with HER2-positive MBC that progressed after treatment with an anthracycline, a taxane, and Trastuzumab were included in this evaluation. The median age was 47.5 years. Of the patients, 34 had distant metastasis (80%), and eight patients (20%) had local relapse. All were pre-treated with Trastuzumab, which was given to 39 patients in the adjuvant setting and to 3 patients in the metastatic setting. The median duration of Trastuzumab treatment was 13 months. The patients received combination Lapatinib 1250 mg per day plus Capecitabine 2000 mg/m2 on days 114- of a 21-day cycle. The primary endpoint was overall response rate (ORR); Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity
The median number of treatment cycles administered was seven cycles. The median duration of follow-up was 14 months. An ORR of 40% was achieved with the Lapatinib and Capecitabine combination. No complete response was observed. Stable disease was achieved in 12 patients (30%). The median PFS was 7.8 months (95% CI, 312-) with a median OS of 10.9 months. The treatment was generally well tolerated. The most common side effects were grade 12- diarrhoea (60%), hand-foot syndrome (50%) and skin eruption (40%). For two patients, the treatment was temporarily discontinued due to grade 3 skin eruption. There were no symptomatic cardiac events observedry endpoints were progression-free survival (PFS), overall survival (OS), and toxicity
Our retrospective evaluation of Lapatinib plus Capecitabine corroborates the findings from the randomized phase III study, E2100. This combination therapy is effective and well tolerated in patients with HER2-positive MBC that has progressed after treatment with anthracycline, a taxane, and Trastuzumab. In our evaluation, 40% of the patients achieved a response to therapy. The median PFS was 7.8 months, and toxicity was mild to moderate(50%) and skin eruption (40%). For two patients, the treatment was temporarily discontinued due to grade 3 skin eruption. There were no symptomatic cardiac events observedry endpoints were progression-free survival (PFS), overall survival (OS), and toxicity