Randomized phase III study of trastuzumab monotherapy followed by docetaxel and trastuzumab versus the combination of trastuzumab and docetaxel as first-line treatment in patients with HER2 positive metastatic breast cancer.

Abstract

Abstract Abstract #3132 Introduction: Treatment with trastuzumab (H) is a standard therapy for the patients with HER2 positive metastatic breast cancer (MBC) and both the combination with H and chemotherapy (CT) and H alone are very popular. However, it is unknown which is better; sequential H alone followed by combination of CT and H at disease progression or the combination with H and CT as first-line therapy. Therefore, we conducted phase III randomized trial compared them in HER2 positive MBC.
 Methods: Eligible patients were HER2 positive MBC patients (pts) with measurable tumour based on RECIST, ECOG Performance status 0 or 1 and left ventricular ejection fraction (LVEF) >50%. Patients with prior CT for MBC, adjuvant H, and Docetaxel (DTX) were excluded. They were randomly assigned to sequential weekly H 2 mg/kg (loading 4 mg/kg) alone followed by combination of DTX (60 mg/m2, q3wks) and H at disease progression (arm A) or concurrent combination of H and DTX (arm B). Primary endpoints were time to progression (TTP) of H alone (arm A) and combination of H and DTX (arm B) and overall survival (OS). Secondary endpoints were overall response rate (ORR), TTP and safety in arm A and B.
 Results:Of the 108 pts registered, 105 pts were eligible. Baseline characteristics of all pts in two groups were well-balanced. Median age was 57/55 years, prior adjuvant CT 38/45% and single metastatic site 30/31% in arm A and B, respectively. Median TTP in arm A was 137 days compared to 445 days in arm B (hazard ratio=4.15; P<0.0001). ORRs were 15% and 71% in arm A and B, respectively. Median OS has not been reached yet, however, the number of deaths were 11 pts in arm A and 4 pts in arm B (hazard ratio=3.36; P=0.028). Adverse event incidence of grade 3 or 4 was 51/85% in each arm. An Efficacy and Safety Evaluation Committee recommended stopping this trial based on the results of TTP and OS.
 Discussion: These results suggested that the combination of H and CT is superior to sequential H alone followed by DTX and H as first-line therapy in HER2 positive MBC pts despite the number of pts did not reach to the planned sample size. We will continue further investigation based on extended follow-up period. The updated data will be presented. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3132.