Long-term safety and efficacy results of two phase II trials indicate that dose-dense anthracycline-based chemotherapy with doxorubicin and cyclophosphamide can be safely combined with anti-HER2 therapy in women with early breast cancer.
Long-term safety and efficacy results of two phase II trials indicate that dose-dense anthracycline-based chemotherapy with doxorubicin and cyclophosphamide can be safely combined with anti-HER2 therapy in women with early breast cancer. Specifically, the trials found that the treatment regimen was associated with a low risk of congestive heart failure.
According to researchers, led by Patrick G. Morris, MD, of Memorial Sloan-Kettering Cancer Center, this result is “clinically relevant given that dose-dense [doxorubicin/cyclophosphamide followed by paclitaxel/trastuzumab] is an appropriate option for patients with HER2-positive early breast cancer as per the current National Comprehensive Cancer Network guidelines.”
Prior research has shown that both anthracyclines and treatments that target HER2 have been associated with an increased risk of cardiotoxicity.
“Since dose-dense chemotherapy is associated with improved patient outcomes compared to conventionally scheduled chemotherapy, we conducted consecutive phase II trials to determine the safety profile of dose-dense chemotherapy and anti-HER2 therapy,” Morris said.
The results of the long-term safety and efficacy outcomes were published in Cancer.
Between January 2005 and May 2008, the researchers enrolled 165 patients with a median age of 46 years. Patients in trial A were given dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab. Patients in trial B had dose-dense paclitaxel substituted for lapatinib. The trial B protocol was eventually deemed to not be feasible because of the high rate of diarrhea noted.
At baseline, 17% of patients had previous hypertension and the median left ventricular ejection fraction was 68%.
“The addition of trastuzumab and lapatinib to sequential dose-dense anthracycline-taxane chemotherapy was associated with a low risk of congestive heart failure and excellent disease control,” Morris said.
At the initial follow-up of 28 months in trial A, only 1 of 70 patients (1.4%) had developed congestive heart failure; at 22 months in trial B, 3 of 95 (3.2%) of patients developed congestive heart failure.
After a median follow-up of 84 months in trial A and 57 months in trial B, only one additional patient was found to have developed congestive heart failure. Therefore, the long-term cardiac event rate for trial A was 1.4% (95% CI, 1.36%–7.7%) and for trial B was 4.2% (95% CI, 1.2%–10.4%).
When looking at the efficacy outcomes, the 5-year distant disease-free survival for patients in trial A was 92% (95% CI, 83%–97%) and for patients in trial B was 89% (95% CI, 81%–94%).
“Follow-up of all studies of adjuvant trastuzumab is ongoing to determine the long-term effects (over several decades) of these therapies in survivors of breast cancer,” the researchers wrote. “The potential benefit of incorporating lapatinib and other novel anti-HER2 agents, such as pertuzumab, into standard regimens is the subject of ongoing phase 3 trials.”