Lapatinib as salvage therapy in metastatic breast cancer: Preliminary results from an expanded access program

Abstract

12006 Background: Lapatinib, a TKI of human epidermal growth factor receptor type 2 (HER2) and epidermal growth factor receptor (EGFR), is active in combination with capecitabine in women with HER2-positive metastatic breast cancer progressing after trastuzumab-based therapy. The primary end point of this single arm, open label trial, was to offer the approval expanded access to lapatinib, in order to provide potential clinical benefit. Secondary objectives were progression free survival, overall survival and evaluation of serious adverse events. Methods: Women affected by locally advanced or metastatic breast cancer with ErbB2 overexpressing tumours, measurable disease and baseline left ventricular ejection fraction ≥ 50% that had progressed after regimens including anthracyclines, taxanes and trastuzumab were included. Since march 2007, 18 patients were enrolled. They received lapatinib at a dosage of 1,250 mg daily continuously plus capecitabine at a dosage of 2,000 mg/m2 on days 1 through 14 of a 21-day cycle. Cardiac function was assessed by ultrasonography at baseline and every three weeks, while objective response was evaluated every six weeks. Results: The principal characteristics of the 18 actually enrolled patients were: median age 54 years (range 42–63), median WHO performance status 1, all with visceral dominant and multiple disease site. To date 12 pts are evaluable for clinical response: 2 partial responses and 6 stable disease were observed; the remaining 4 pts progressed. Median duration of survival was 6+ months (range 4–9+). Toxicity consisted mainly in grade I-II asthenia in 5 pts and grade I-II hand-foot syndrome in 6 pts. Gastroenteric toxicity affected 4 pts. As to concer cardiac toxicity, two patients developed an asymptomatic decline of left ventricular ejection fraction below 50% and withdrawn the treatment. Conclusions: These preliminary data show the activity of lapatinib in previous heavily treated metastatic breast cancer. Further lapatinib-cytotoxic combinations are warranted. No significant financial relationships to disclose.