Clinical Activity of Trastuzumab and Vinorelbine in Women With HER2-Overexpressing Metastatic Breast Cancer

• DOI: 10.1200/jco.2001.19.10.2722
• Publication Date: 2017-02-24T07:20:52Z
• Authors: Harold J. Burstein; Irene Kuter; Susana M. Campos; Rebecca S. Gelman; Laura Tribou; Leroy M. Parker; Judith Manola; Jerry Younger; Ursula Matulonis; Craig A. Bunnell; Ann H. Partridge; Paul G. Richardson; Kathryn Clarke; Lawrence N. Shulman; Eric P. Winer
• Keywords: Adult; Receptor, ErbB-2; Antibodies, Monoclonal; Breast Neoplasms; Vinorelbine; Middle Aged; Trastuzumab; Antibodies, Monoclonal, Humanized; Vinblastine; 3. Good health; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Chemotherapy, Adjuvant; Antineoplastic Combined Chemotherapy Protocols; Humans; Female; Neoplasm Metastasis; Cardiomyopathies; Aged

PURPOSE: To determine the response rate and toxicity profile of trastuzumab administered concurrently with weekly vinorelbine in women with HER2-overexpressing advanced breast cancer. PATIENTS AND METHODS: Forty women with HER2-positive (+3 by immunohistochemistry, n = 30; +2 or positive, n = 10) breast cancer were enrolled onto a study of trastuzumab (4 mg/kg × 1, 2 mg/kg weekly thereafter) and vinorelbine (25 mg/m2 weekly, with dose adjusted each week for neutrophil count). Eighty-two percent of women had received prior chemotherapy as part of adjuvant (30%), metastatic (25%), or 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 rate, 75%, conditional corrected 95% confidence interval, 57% to 89%). The response rate was 84% in patients treated with trastuzumab and vinorelbine as first-line therapy for metastatic disease, and 80% among HER2 +3 positive patients. High response rates were also seen in women treated with second- or third-line therapy, and among patients previously treated with anthracyclines and/or taxanes. Combination therapy was feasible; patients received concurrent trastuzumab and vinorelbine in 93% of treatment weeks. Neutropenia was the only grade 4 toxicity. No patients had 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 tolerated.