Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer

Purpose: To determine the response rate and toxicity profile of trastuzumab administered concurrently with weekly vinorelbine in women with HER2-overe xpressing advanced breast cancer. Patients and Methods: Forty women with HER2-positive (+3 by immunohistochem istry, n = 30; +2 or positive, n = 10) breast cancer were enrolled onto a s tudy of trastuzumab (4 mg/kg x 1, 2 mg/kg weekly thereafter) and vinorelbin e (25 mg/m(2) weekly, with dose adjusted each week for neutrophil count). E ighty-two percent of women had received prior chemotherapy as part of adjuv ant (30%), metastatic (25%), oh both (28%) treatment, including substantial portions of patients who had previously received either anthracyclines (20 %), taxanes (15%), or both types (38%) of chemotherapy. Results: Responses were observed in 30 of 40 patients (overall response rat e, 75%, conditional corrected 95% confidence interval, 57% to 89%). The res ponse rate was 84% in patients treated with trastuzumab and vinorelbine as first-line therapy for metastatic disease, and 80% among HER2 +3 positive p atients. High response rates were also seen in women treated with second- o r third-line therapy, and among patients previously treated with anthracycl ines and/or taxanes. Combination therapy was feasible; patients received co ncurrent trastuzumab and vinorelbine in 93% of treatment weeks. Neutropenia was the only grade 4 toxicity. No patients herd symptomatic heart failure. Grade 2 cardiac toxicity was observed in three patients. Prior cumulative doxorubicin dose in excess of 240 mg/m2 and borderline pre-existing cardiac function were associated with grade 2 cardiac toxicity. Conclusion: Trastuzumab in combination with vinorelbine is highly active in women with HER2-overexpressing advanced breast cancer and is well tolerate d. (C) 2001 by American Society of Clinical Oncology.