An intense dose-dense chemotherapy approach offers better survival than standard therapy, extending out to 10 years in women with breast cancer and extensive axillary lymph node involvement, according to the long-term results of the AGO study.
“Dose-dense, intense dose-dense regimens, or tailored dose-dense regimens have shown superior clinical outcomes when compared with conventionally dosed chemotherapy,” wrote study authors led by Volker J. Möbus, MD, of the Academic Hospital of the Goethe University Frankfurt in Germany. “However, clinical follow-up has been relatively short in these studies, and long-term clinical outcome data are missing.”
This analysis was a 10-year follow-up report from the AGO trial, which included 1,284 patients with high-risk breast cancer. All patients had four or more involved axillary lymph nodes, and were randomized to receive either 3 courses each of intense dose-dense sequential epirubicin, paclitaxel, and cyclophosphamide (iddEPC; 658 patients), or standard epirubicin/cyclophosphamide followed by paclitaxel (EC-P; 626 patients). Results were published in Annals of Oncology.
After a median follow-up of 122 months, both event-free survival (EFS) and overall survival (OS) were better with iddEPC. The EFS rate for iddEPC was 56% at 10 years, compared with 47% with EC-P, for an adjusted hazard ratio (HR) of 0.74 (95% CI, 0.63–0.87; P = .00014). The OS rates at 10 years were 69% with iddEPC and 59% with EC-P, for an HR of 0.72 (95% CI, 0.60–0.87; P = .0007).
This effect was more pronounced with more lymph node involvement. Patients with more than 10 positive axillary lymph nodes had an OS rate at 10 years of 62% with iddEPC and 48% with EC-P, for an HR of 0.66 (P = .0016); for those with 4 to 9 positive lymph nodes, the OS rates were 74% and 66%, respectively, for an HR of 0.77 (P = .061). The authors noted that the benefit seen with iddEPC was independent of HER2 and estrogen receptor status.
A secondary neoplasm was observed in 46 patients. There were 11 cases of acute myeloid leukemia or myelodysplastic syndrome, including 9 in the iddEPC group and 2 in the EC-P group (P = .065).
Hematologic toxicity was more frequent in the iddEPC group—7% vs 2% in EC-P patients (P < .0001). Only 6 EC-P patients needed a red blood cell transfusion, compared with 127 (20%) in the iddEPC group (P < .0001). Nonhematologic toxicity was also more frequent in the intense dose-dense group, but grade 3/4 toxicities were relatively rare and “clinically acceptable.”
“Independently of known molecular breast cancer subtypes, dose-dense chemotherapy remains an important treatment option for high-risk breast cancer patients,” the authors concluded. “Future research will need to focus on identifying biomarkers that predict treatment response and will need to evaluate combination therapies with novel targeted agents to further improve treatment outcomes for patients diagnosed with high-risk primary breast cancer.”