Sara A. Hurvitz, MD
The cardiotoxicity risk associated with anthracycline regimens for patients with breast cancer has led to a debate among physicians over the use of these therapies.
“Some physicians feel you should not worry about heart risk for patients when the risks themselves tend to be less than 5% in the short term,” explained Sara A. Hurvitz, MD, who discussed the pros and cons of anthracycline treatment in a talk at the 2017 Miami Breast Cancer Conference.
Other physicians worry about their use, Hurvitz said, because they argue that the long-term risks of anthracyclines tend to be unknown because there are few, if any, studies that follow the women long term.
The BCIRG 006 study compared anthracycline regimens with nonanthracycline regimens. The trial aimed to describe and compare health-related quality of life in patients with high-risk, node-negative, HER2-positive early breast cancer receiving docetaxel and trastuzumab (Herceptin)–based regimens compared with docetaxel-based regimens alone. The main safety concern with trastuzumab-based regimens, particularly in combination with anthracyclines, is the cardiotoxicity. The BCIRG 006 study was one of few adjuvant trastuzumab trials to include a nonanthracycline arm to compare these cardiotoxicities.
There were 3 treatment arms in the study: (1) 60 mg/m2
of adjuvant doxorubicin and 600 mg/m2
of cyclophosphamide every 3 weeks for 4 cycles followed by 100 mg/m2
of docetaxel for 4 cycles; (2) cyclophosphamide and doxorubicin followed by docetaxel with 4-mg/kg loading dose and 2 mg/kg weekly of trastuzumab during chemotherapy and 6 mg/kg every 3 weeks after chemotherapy for 1 year; and (3) 6 cycles of carboplatin and 75 mg/m2
of docetaxel every 3 weeks with trastuzumab for 1 year.
The 2 distinct trastuzumab-containing regimens in the BCIRG 006 trial, 1 with and 1 without an anthracycline base, demonstrated improved survival with a more favorable safety profile. Although anthracyclines are a standard therapy in the treatment of adjuvant breast cancer, the cardiac and marrow toxicity risks affect long-term use, whereas the nonanthracycline regimen resulted in better adverse event change scores at the end of chemotherapy, and better health-related quality-of-life findings.1
The cardiotoxicity related to anthracyclines has been shown to be dose-dependent, occurring more frequently with higher doses than with doses administered in the adjuvant setting. However, some acute cardiac events can occur after the first dose.
An additional serious adverse event related to anthracyclines is the development of myelodysplastic syndrome (MDS) and acute myelogenous leukemia. Multiple cytotoxic agents, such as cyclophosphamide, doxorubicin, daunorubicin, and epirubicin, have been implicated.
“The benefits of using these nonanthracycline-based regimens is they have been consistently shown to be relatively safe in terms of the cardiac safety perspective,” Hurvitz said.
Another trial that compared an anthracycline with a nonanthracycline regimen was the MA.5 trial. The trial enrolled 710 patients with node-positive breast cancer who were randomly assigned to receive cyclophosphamide/epirubicin/fluorouracil or cyclophosphamide/methotrexate/fluorouracil.2
Although this trial was completed many years ago, the nonanthracycline regimen is still frequently used in patients who are not candidates for anthracycline-based regimens.
In an interview with OncLive
, Hurvitz, director of the Hematology/ Oncology Breast Cancer Program and an associate professor in the Department of Medicine at the University of California, Los Angeles, discussed anthracycline versus nonanthracycline treatments for patients with breast cancer.Where do we stand on exploring the potential to omit anthracyclines in adjuvant treatment for patients with breast cancer?Hurvitz:
There have been a few studies relating the relative efficacy of anthracycline-and- trastuzumab–based regimens versus a nonanthracycline regimen. The typical docetaxel/carboplatin/trastuzumab regimen is the backbone that has been studied in about 5000 patients in different clinical trials. There is a more recent regimen of weekly paclitaxel and trastuzumab that Sara M. Tolaney, MD, evaluated for small, lymph node–negative tumors. Then another regimen of docetaxel/Cytoxan/trastuzumab was evaluated by Stephen E. Jones, MD.What are the benefits of nonanthracycline–based regimens?