Phase II study of lapatinib in combination with vinorelbine in patients with ErbB2-amplified recurrent or metastatic breast cancer.

Abstract

e13079 Background: There is a need for new treatment options in ErbB2 amplified advanced breast cancer.Limited efficacy and safety data has been reported for a lapatinib (LAP) and vinorelbine (VNL) combination in this setting. This is a multicenter, phase II study of LAP in combination with VNL in women with ErbB2 positive metastatic or recurrent breast cancer who have received prior taxane and/or antracycline. Methods: Patients received 1250mg oral LAP continously once daily and VNL 25 mg/sqm IV in the first 6 pts, and 20 mg/sqm IV on D1 and D8 every 3 week after neutropenia was identified as a DLT. The primary endpoints of the study are response rate and toxicity. Secondary endpoints include progression free survival(PFS) and duration of response. 29 pts were planned and enrolled. RECISTis used for response and NCI-CTCAE is used for adverse events evaluation. We present here the combined results of both VNL doses (6 pts for 25 mg/m2 and 15 pts for 20 mg/m2). Median age of the pts was 60 years (range 33-75). Prior trastuzumab was used in 86% of the pts. Patients with brain metastases without symptoms were included. Results: Median number of prior chemotherapy regimens was 2 (range 1-4). Nineteen pts were evaluable for response. Median follow up was 28,5 weeks(range 7,5-80,5) and 13 patients progressed during this period. Five of 19 patients (26%; 95% CI 9,15-51,2) had partial response and 8 patients (42%; 95% CI 20,25-66,50) had stable disease. The median PFS was 20 weeks (95% CI (12,14-27,86). 21 pts and 120 cycles were evaluated for toxicity. Median number of treatment cycles was 4(range, 2-18 cycles). Grade 3-4 neutropenia without fever in 13 patients(62%), grade 3-4 leukopenia in 4 pts (19%), grade 3 anemia in 1 pt (5%), febrile neutropenia in 1 pt (5%). The most common non-hematologic grade 3 adverse events were adinamia in 3(14%), stomatitis and diarrhea in 2 (10%), insomnia, motor neuropathy, anorexia, abdominal pain, hepatotoxicity, constipation, infection and respiratory distress in1(5%) of the pts. Conclusions: The VNL and LAP combination at 1250mg LAP continously oral once daily and VNL 20 mg/sqm dose is a tolerable alternative for pts with ErbB2 + metastatic breast cancer.