As reported in the Journal of Clinical Oncology by Delaloge et al, a second randomized component of the phase III EORTC 10041/BIG 3-04 MINDACT trial, though underpowered, suggested no benefit of docetaxel/capecitabine vs standard anthracycline-based adjuvant therapy for patients with early breast cancer at high clinical risk and/or high genomic risk.
The initial report from MINDACT showed that patients with early breast cancer at high clinical but low genomic risk (on the basis of MammaPrint) could safely avoid adjuvant chemotherapy.
Study Details
In the second randomization of the trial, 1,301 patients were randomly assigned to receive a standard anthracycline-based regimen with or without taxanes (control group, n = 649) or 75 mg/m2 of docetaxel plus 825 mg/m2 of capecitabine twice daily for 14 days every 3 weeks for six cycles (experimental group, n = 652). The primary endpoint was disease-free survival.
Among all patients, 60.5% were categorized as having clinical high-risk and genomic high-risk disease; 27.0% as clinical high-risk/genomic low-risk; 10.5% as clinical low-risk/genomic high-risk; and 2.0% as clinical low-risk/genomic low-risk disease. In the control group, 29.6% of patients received taxanes.
Disease-Free Survival
KEY POINTS
- The study was underpowered for definitive analysis.
- No difference in disease-free survival was observed for docetaxel/capecitabine vs anthracycline-based adjuvant therapy.
The total number of disease-free survival events observed (n = 148) was lower than that required for definitive analysis (n = 422), due to lower-than-expected accrual and event rates. Among all patients, after 5-year median follow-up, disease-free survival was 90.7% in the control group vs 88.8% in the experimental group (hazard ratio [HR] = 0.83, P = .26). In the clinical high-risk/genomic high-risk subgroup, no differences between control and experimental groups were observed in 5-year overall survival (96.2% vs 96.3%, HR = 0.91, 95% confidence interval [CI] =0.54–1.53) or 5-year disease-free survival (86.1% vs 88.1%, HR = 0.83, 95% CI = 0.58–1.21).
Adverse Events
The docetaxel/capecitabine group had more reported grade 1 neuropathy (27.1% vs 11.2%), grade 2 hand/foot syndrome (28.5% vs 3.3%), and grade 2 diarrhea (13.7% vs 5.8%). The control group had more reported grade 2 anemia (14.2% vs 5.1%) and grade 4 neutropenia (24.6% vs 20.5%). Serious cardiac events occurred in five patients in the docetaxel/capecitabine group vs four patients in the control group. Second cancers occurred in 21 patients in the docetaxel/capecitabine group vs 32 in the control group. Death considered related to treatment occurred in three vs two patients.
The investigators concluded: “Although underpowered, this second randomization in MINDACT did not show any improvement in outcome or safety with the use of [docetaxel/capecitabine] compared with anthracycline-based chemotherapy.”
Suzette Delaloge, MD, of the Department of Medical Oncology, Gustave Roussy, Villejuif, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the European Commission Framework Programme VI, Breast Cancer Research Foundation, National Cancer Institute, Novartis, F. Hoffman La Roche, Sanofi, Eli Lilly, Veridex, and others. For full disclosures of the study authors, visit ascopubs.org.
