SAN ANTONIO – Six cycles of adjuvant chemotherapy provided no added benefit over four in breast cancer patients with zero to three positive axillary lymph nodes in the Cancer and Leukemia Group B 40101 trial.
Dr. Lawrence N. Shulman
The 2-by-2 factorial design of CALGB 40101 aimed to address two key questions: the optimal duration of chemotherapy in patients with good-prognosis breast cancer, and the merits of paclitaxel- vs. anthracycline-based chemotherapy, long the backbone of adjuvant chemotherapy for breast cancer, Dr. Lawrence N. Shulman explained at the San Antonio Breast Cancer Symposium.
The data regarding the paclitaxel vs. doxorubicin-plus-cyclophosphamide comparison aren’t yet available for analysis, although the study’s data safety and monitoring board has indicated that the two regimens were equivalent. With regard to the optimal duration of adjuvant chemotherapy, however, the results are in – and longer is not better in this patient population, according to Dr. Shulman, chief medical officer and senior vice president for medical affairs at the Dana-Farber Cancer Institute in Boston.
The treatment-duration analysis involved 3,173 patients with operable breast cancer and zero to three positive axillary nodes. They were randomized first to either paclitaxel or doxorubicin/cyclophosphamide, and then further randomized to four or six cycles of their assigned chemotherapy. Most patients received the chemotherapy every 2 weeks.
With a median follow-up of 4.6 years, the relapse-free survival rate in patients who received six cycles of chemotherapy was 91.6% and closely similar at 91.8% in those who got four cycles. The overall survival rate was 95.3% in the six-cycle group, compared with 96.4% with four cycles, again a statistically similar outcome. Subset analyses showed no differential impact for chemotherapy duration based upon tumor estrogen receptor or HER2 status.
Grade 3/4 anemia, neutropenia, and fever were more frequent in the two anthracycline-based chemotherapy arms. Grade 3 neuropathy occurred only in the paclitaxel-treated patients, with rates of 6% in those who got four cycles and 13% with six. Grade 3-5 cardiac toxicity occurred in only 10 of the 3,173 patients, 7 of whom were in the anthracycline group.
Audience members hailed CALGB 40101 as an important study because it’s one of very few trials to examine duration of chemotherapy as a key variable.
Dr. Shulman said it’s possible that the six-cycle chemotherapy regimen will eventually pay off in terms of fewer distant metastases in this good-prognosis group of patients. Time will tell. But to date there have been 50 breast cancer–related deaths in the six-cycle treatment group and only 41 in those who got four cycles.
He declared having no relevant financial relationships.