Phase II study of lapatinib and tegafur combination efficacy for the treatment of HER2+ metastatic breast cancer.

e11086 Background: One of effective ways to overcome resistance to trastusumab is to prescribe lapatinib, an inhibitor of ErbB1 and ErbB2 receptors, in combination with capecitabine, a fluopirimidine cytostatic agent. We examined the efficacy and safety of combination of lapatinib plus tegafur, another oral fluopirimidine, in patients with ErbB2-positive metastatic breast cancer (MBC). Methods: 13 patients with HER2+ MBC were enrolled into the study. 11 patients were analyzed, as 2 women had been included into the study too late to be assessed. Median age was 43.5 years. All patients had previously received trastuzumab for MBC, 92% of patients had been treated with taxanes, 77% - with anthracyclines, and 31% received capecitabine. 69% of patients were treated with more than 2 lines of chemotherapy for MBC. The study included 4 patients with CNS metastases. During the study, the patients received lapatinib 1250 mg/day and tegafur 1200 mg/day, days 1-21, with 3-week intervals. Results: 1 patient achieved and still is in partial response which has been lasting for 5 months, while disease stabilization was observed in 9 out of 10 cases. The clinical benefit rate in this trial was 90%. There was 1 case of the disease progression. At the time of analysis median TTP was 10.1 months (95%CI 6-13). The combination of lapatinib and tegafur was effective in 4 out of 5 patients with CNS metastases. There were no adverse events greater than grade I observed on lapatinib plus tegafur therapy. Diarrhea was the most common adverse event, but it did not compromise the patients' quality of life. Conclusions: The lapatinib plus tegafur combination is a promising option for treatment of patients with HER2+ MBC after progression on trastuzumab-containing therapy. This mode was acceptable for patients who had received 2 or more lines of previous therapy. The combination was well tolerated by the patients. Both agents being oral formulations, the treatment mode is quite suitable for outpatient use.