Final results of a first line multicenter phase II metastatic breast cancer trial of vinflunine monotherapy and in combination with trastuzumab in HER2+ patients.

Purpose: Trastuzumab-based therapy improves survival for women with human epidermal growth factor receptor 2 (HER2)–positive advanced breast cancer. We conducted a multicenter phase II study to evaluate the efficacy and safety of trastuzumab combined with vinorelbine, and to assess cardiac surveillance algorithms and tumor markers as prognostic tools. Patients and Methods: Patients with HER2-positive (immunohistochemistry [IHC] 3+-positive or fluorescence in situ hybridization [FISH]-positive) metastatic breast cancer received first-line chemotherapy with trastuzumab and vinorelbine to determine response rate. Eligibility criteria were measurable disease and baseline ejection fraction ≥ 50%. Serial testing for HER2 extracellular domain (ECD) was performed. Results: Fifty-four women from 17 participating centers were entered onto the study. The overall response rate was 68% (95% confidence interval, 54% to 80%). Response rates were not affected by method of HER2 status determination (FISH v IHC) or by prior adjuvant chemotherapy. Median time to treatment failure was 5.6 months; 38% of patients were progression free after 1 year. Concurrent therapy was quite feasible with maintained dose-intensity. Patients received both chemotherapy and trastuzumab on 90% of scheduled treatment dates. Two patients experienced cardiotoxicity in excess of grade 1; one patient experienced symptomatic heart failure. A surveillance algorithm of screening left ventricular ejection fraction (LVEF) at 16 weeks successfully identified women at risk for experiencing cardiotoxicity. Other acute and chronic side effects were tolerable. Lack of decline in HER2 ECD during cycle 1 predicted tumor progression. Conclusion: Trastuzumab and vinorelbine constitute effective and well-tolerated first-line treatment for HER2-positive metastatic breast cancer. Patients with normal LVEF can be observed with surveillance of LVEF at 16 weeks to identify those at risk for cardiotoxicity.

Download Full-text

Abstract P4-12-08: Final efficacy results from a single-arm multicenter phase II study evaluating first-line trastuzumab, bevacizumab, and capecitabine (HAX) therapy for HER2-positive locally recurrent/metastatic breast cancer (LR/mBC)

10.1158/0008-5472.sabcs13-p4-12-08 ◽

2013 ◽

Author(s):

M Martín ◽

A Makhson ◽

J Gligorov ◽

M Lichinitser ◽

A Lluch ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Metastatic Breast ◽

First Line ◽

Her2 Positive ◽

Multicenter Phase ◽

Locally Recurrent

Download Full-text

A multicenter phase II study of epirubicin (E) with low-dose herceptin (LD-H) as a first-line treatment in HER2 overexpressing metastatic breast cancer (MBC)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1060 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 1060-1060 ◽

Cited By ~ 1

Author(s):

M. De Tursi ◽

C. Carella ◽

E. Ricevuto ◽

A. Gennari ◽

C. Orlandini ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Phase Ii ◽

Low Dose ◽

Phase Ii Study ◽

Metastatic Breast ◽

Left Ventricular Ejection ◽

First Line ◽

Multicenter Phase ◽

Her 2

1060 Background: The combination of doxorubicin and herceptin (H) has been proven to be an effective regimen in metastatic breast cancer (MBC), although it was associated with an increased risk of cardiotoxicity. Methods: The aim of this study was to evaluate cardiac safety and efficacy of epirubicin (E) in combination with low-dose herceptin (LD-H) as first-line chemotherapy for women with HER-2 positive MBC. Forty-five patients were enrolled in a two-step, multicenter phase II study. In the first step, H was given at 2 mg/Kg loading dose on day 1, followed by 1 mg/Kg weekly; in the second step (≥ 12 objective responses/21pts), H dose was maintained at 1 mg/kg weekly. E was administered at 90 mg/m2 on day 1 every 3 weeks. After 6–8 courses, H was continued as a single agent for a maximum of 52 weeks. To assess cardiotoxicity, patients were evaluated for the left ventricular ejection fraction (LVEF) at baseline, every two cycles during E and LD-H, and every three months during LD-H alone. Cardiotoxicity was defined as signs or symptoms of congestive heart failure in = 10% of patients at an E dose of 720 mg/ m2 or in = 20% of patients at an E dose > 720 < 1,000 mg/m2. Results: Eight episodes of cardiotoxicity were observed (an asymptomatic decrease in LVEF =15% in 6 patients and an asymptomatic decline of LVEF at = 50% in 2 patients). Grade 3–4 neutropenia, alopecia and thrombocytopenia occurred in 25%, 45.5% and 6.8% of patients, respectively. Complete and partial responses were 2.4 and 61.9%, respectively, for an overall response rate of 64.3%. The median time to progression was 8.2 months (95% CI, 5.2–9.2 months) and the median overall survival was 32.8 months (95% CI, 17.1–48.6 months). Conclusions: E plus LD-H is an active treatment regimen for HER-2 positive MBC and demonstrates a very favourable safety profile, with manageable cardiotoxicity. No significant financial relationships to disclose.

Download Full-text