(CHICAGO, IL) – Adding bevacizumab to first-line chemotherapy and trastuzumab was safe and well tolerated in patients with HER2+ metastatic breast cancer; however, no significant differences in clinical benefit or measurements in circulating tumor cells (CTCs) were observed, according to results of a phase 3 clinical trial presented at the 2012 American Society of Clinical Oncology Annual Meeting.
Previously reported preclinical and nonrandomized clinical data had suggested therapeutic synergy may exist when bevacizumab (Avastin) and trastuzumab (Herceptin) are combined, according to Ingrid A. Mayer, MD, MSCI, Director, Clinical Core of Breast Cancer Program, Vanderbilt-Ingram Cancer Center, Nashville, TN.
In the induction phase, the Eastern Cooperative Oncology Group study randomly assigned patients to trastuzumab 2mg/kg + paclitaxel 80mg/m2 ± carboplatin AUC 2 on Days 1, 8 and 15 and either placebo or bevacizumab 10mg/kg every 2 weeks for a total of 24 weeks. Maintenance therapy with trastuzumab/placebo or trastuzumab/bevacizumab was then continued without chemotherapy every 3 weeks until disease progression or unacceptable toxicity. Disease assessments were performed every 3 months. A total of 48 patients were accrued in each of the 2 study arms.
After a median follow-up time of 30 months, adding bevacizumab to first-line trastuzumab + paclitaxel with or without carboplatin chemotherapy yielded no significant difference in median progression-free survival (PFS) vs placebo. Placebo was associated with an 11.1-month PFS and bevacizumab, a 12.2-month PFS (HR=0.65; P=0.10). Analysis of CTC and PFS (<5 vs ≥5) showed no difference (HR=0.91; P=0.77).
Best response was five complete responses in each of the placebo and bevacizumab groups, 20 partial responses in each of the groups; and 13 patients had stable disease in the placebo group vs nine in the bevacizumab group.
Grade 3 hypertension was noted in 11% of patients in both the placebo-arm group and bevacizumab group. Grade 3/4 adverse events seen in bevacizumab-arm patients that were not seen among placebo-arm patients included left ventricle systolic dysfunction (9% vs 0), cardiomyopathy (2% vs 0), and proteinuria (4% vs 2%) but bevacizumab did not significantly increase treatment toxicity and “was overall safe and well tolerated,” Dr. Mayer noted.
The study was terminated in 2009 due to poor study participant accrual.
This article originally appeared on MPR