Four cycles of docetaxel/cyclophosphamide (TC) plus trastuzumab is safe, with a low rate of cardiac events, in the adjuvant treatment of low-risk patients with HER2-positive breast cancer, according to the results of a Phase II trial of 260 women followed for at least one year.
This poster presentation by Stephen E. Jones, MD, Medical Director of US Oncology Research, and colleagues at the CTRC-AACR San Antonio Breast Cancer Symposium is the latest in a series of analyses pointing to the efficacy and safety of the regimen.
At the 2007 San Antonio meeting, Dr. Jones and colleagues reported that docetaxel and cyclophosphamide is associated with better disease-free survival and overall survival rates than doxorubicin and cyclophosphamide in the adjuvant treatment of older as well as younger patients with early breast cancer.
Then, at the 2008 meeting, the researchers reported the regimen to be well tolerated in the short term. This latest analysis extends those safety findings out to a median of 18 months, the researchers reported.
“Although the addition of trastuzumab to anthracycline-based adjuvant regimens has proven effective, it is associated with increased cardiac toxicity. Therefore, a short course of the nonanthracycline TC regimen coupled with trastuzumab appeared to be a logical combination for women with lower-risk HER2-positive breast cancer,” Dr. Jones said.
The primary objective of the most recent analysis was to determine the cardiac safety of four cycles of TC combined with one year of trastuzumab in patients with HER2-positive early breast cancer.
The analysis involved 263 patients with operable, histologically confirmed, invasive carcinoma of the breast and HER2-positivity confirmed by immunohistochemistry or fluorescence in-situ hybridization. Patients with node-negative disease or with Stage T1 or T2 breast cancer and one to three positive nodes were eligible.
All patients had normal cardiac function as evidenced by a left ventricular ejection fraction greater than 50% at the time of registration. The median baseline LVEF was 64%.
The median age of the patients was 55 years; 90% had an Eastern Cooperative Oncology Group performance status of 0, and the rest had a performance status of 1. Two-thirds of patients had estrogen receptor-positive tumors, nearly half had progesterone-receptor-positive tumors, and 77% had no node involvement.
On Day 1 of each 21-day cycle for a total of four cycles, patients received 75 mg/m2 of intravenous docetaxel, followed by 600 mg/m2 of IV cyclophosphamide. Weekly trastuzumab was given as a 4 mg/kg IV loading dose, over 90 minutes, on Day 1 of Cycle 1 only, followed by 2 mg/kg IV on Days 8 and 15 of the first cycle and on Days 1, 8, and 15 of each cycle thereafter, throughout chemotherapy.
Beginning seven days after Day 15 of the last cycle, trastuzumab was administered at a dose of 6 mg/kg IV every three weeks to complete 12 months of therapy.
Treatment Well Tolerated
The median follow-up time was 17.9 months. A total of 78.3% of patients completed one year of treatment, and 11 (4.2%) remained on treatment at one year.
Forty-six (17.5%) of patients discontinued treatment, 27 (10.3%) due to toxicities. Sixteen of these patients dropped out due to noncardiac toxicity and 11 due to cardiac toxicity—nine due to drops in ejection fraction, one due to bradycardia and syncope, and one due to chest pain.
No cases of congestive heart failure were observed.
The bottom line, Dr. Jones reported, is that TC plus trastuzumab has a low rate of associated cardiac events.
Plus, he said, the schedule is relatively easy for patients, as they are done with chemotherapy after 12 weeks.
The findings are in line with those of Dennis J. Slamon, MD, PhD, who said his own study also showed that a nonanthracycline-based regimen is just as effective, with less cardiac toxicity, than an anthracycline-based regimen (see article on next page).
“At this point, if a patient is HER2-positive, we should treat her with trastuzumab and a non-anthracycline regimen. We'll get just as good efficacy without cardiac problems,” said Dr. Slamon, Chief of the Division of Hematology/ Oncology at the University of California Los Angeles and Director of Clinical/Translational Research and Director of the Revlon/UCLA Women's Cancer Research Program.