Trastuzumab and Vinorelbine as First-Line Therapy for HER2-Overexpressing Metastatic Breast Cancer: Multicenter Phase II Trial With Clinical Outcomes, Analysis of Serum Tumor Markers as Predictive Factors, and Cardiac Surveillance Algorithm

Abstract

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.

Vinorelbine plus trastuzumab combination as first-line therapy for HER 2-positive metastatic breast cancer patients: an international phase II trial

“…In the study by Marty et al (2005), one patient (1%) receiving trastuzumab and docetaxel experienced symptomatic heart failure, and another patient experienced symptomatic heart failure 5 months after discontinuation of trastuzumab while receiving an investigational anthracycline for 4 months. The favourable safety profile of the vinorelbine/trastuzumab combination has been observed in other trials: Burstein et al (2003) reported only one patient with grade 3 cardiac toxicity, whereas no grade 3 -4 cardiac toxicity was seen by Jahanzeb et al (2002).…”

“…Burstein reported 75% of response rates without grade 3 -4 cardiac toxicity in a single centre trial of weekly vinorelbine (25 mg m À2 ) and trastuzumab (4 mg kg À1 on day 1 then 2 mg kg À1 week À1 ) used as first-and second-line therapy (Burstein et al, 2001). In a multiinstitutional trial of the same schedule, the same author confirmed the efficacy of trastuzumab plus vinorelbine as first-line chemotherapy, with 68% of patients achieving an objective response and 39% of patients remaining free of disease progression at 1 year (Burstein et al, 2003). Jahanzeb et al (2002), in a trial of first-line vinorelbine and trastuzumab at the same schedule and doses as the current study, reported 78% of responses among 40 patients.…”

“…Several phase II studies have been conducted in the first-line setting or after progression to other chemotherapy. This doublet has produced consistent response rates ranging from 60 to 86%, with a satisfactory tolerance profile (Burstein et al, 2001(Burstein et al, , 2003Jahanzeb et al, 2002;Bernardo et al, 2004;Bayo-Calero et al, 2004).…”

“…Several single institution or national phase II trials have been conducted with this regimen as first-line therapy or in heavily pretreated patients with metastatic breast cancer. These studies consistently demonstrated high efficacy with limited toxicities (Burstein et al, 2001(Burstein et al, , 2003Jahanzeb et al, 2002;Bayo-Calero et al, 2004;Bernardo et al, 2004).…”

Targeting the function of the HER2 oncogene in human cancer therapeutics

“…The most beneficial clinical use of trastuzumab has been in combination with various cytotoxic chemotherapies. The addition of trastuzumab to multiple chemotherapy regimens significantly increases their antitumor efficacy (Slamon et al, 2001;Burstein et al, 2003;Marty et al, 2005). The biggest impact of trastuzumab has been in the treatment of patients with potentially curable early-stage breast cancer.…”