Phase II Trial of Weekly Vinorelbine and Trastuzumab as First-Line Therapy in Patients with HER2+ Metastatic Breast Cancer

Abstract

Abstract Learning Objectives After completing this course, the reader will be able to: Summarize the epidemiology and natural history of HER2+ breast cancer.Differentiate the two primary methods for measuring HER2 in breast cancer patients.Appreciate the rationale for investigating vinorelbine in combination with trastuzumab.Discuss the relative efficacy and safety of trastuzumab and vinorelbine in HER2+ breast cancer. Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com Purpose. Human epidermal growth factor receptor 2 (HER2) overexpression is associated with a more aggressive form of breast cancer that responds well to trastuzumab therapy. Trastuzumab-based combination regimens have shown greater antitumor activity than chemotherapy alone. These findings, coupled with the favorable antitumor activity and tolerability profile of vinorelbine in breast cancer, provided the rationale for investigating the novel combination of vinorelbine and trastuzumab. Patients and Methods. A phase II, open-label trial of intravenous vinorelbine (30 mg/m2 on day 1, then weekly) and trastuzumab (4 mg/kg on day 0, then 2 mg/kg weekly) was conducted in previously untreated HER2+ metastatic breast cancer patients. Vinorelbine dose was adjusted for grade 3/4 neutropenia; patients remained on combination therapy until disease progression or patient withdrawal due to adverse events. Results. Of 40 enrolled patients (median age 51 years, range 30-82), 37 were evaluable for response. Overall response rate was 78% (29/37, 95% confidence interval [CI] 62%-90%), including four (11%, 95% CI 3%-25%) complete and 25 (68%) partial responses. Objective tumor response correlated with degree of HER2 positivity: immunohistochemistry (IHC) 3+ = 82% (18/22) response and IHC 2+ = 58% (7/12) response. Median time to progression was 72 weeks (95% CI 37-138 weeks); median survival has not been reached. Grade 3/4 neutropenia was the most frequent serious toxicity and cause of dose reductions (9% of courses) and omissions (10% of courses). No patient experienced serious cardiac toxicity. Conclusions. Weekly vinorelbine/trastuzumab offers a high therapeutic index as initial therapy in patients with HER2+ metastatic breast cancer. Further investigation of this novel regimen is planned.