1. Standard Anthracycline Based Versus Docetaxel-Capecitabine in Early High Clinical and/or Genomic Risk Breast Cancer in the EORTC 10041/BIG 3-04 MINDACT Phase III Trial.
- Author
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Delaloge, Suzette, Piccart, Martine, Rutgers, Emiel, Litière, Saskia, van 't Veer, Laura J, van den Berkmortel, Franchette, Brain, Etienne, Dudek-Peric, Aleksandra, Gil-Gil, Miguel, Gomez, Patricia, Hilbers, Florentine S, Khalil, Zaman, Knox, Susan, Kuemmel, Sherko, Kunz, Georg, Lesur, Anne, Pierga, Jean-Yves, Ravdin, Peter, Rubio, Isabel T, Saghatchian, Mahasti, Smilde, Tineke J, Thompson, Alastair M, Viale, Giuseppe, Zoppoli, Gabriele, Vuylsteke, Peter, Tryfonidis, Konstantinos, Poncet, Coralie, Bogaerts, Jan, and Cardoso, Fatima
- Subjects
Genetics ,Rare Diseases ,Breast Cancer ,Clinical Trials and Supportive Activities ,Human Genome ,Cancer ,Clinical Research ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Adult ,Aged ,Aged ,80 and over ,Anthracyclines ,Antineoplastic Combined Chemotherapy Protocols ,Breast Neoplasms ,Capecitabine ,Docetaxel ,Female ,Humans ,Middle Aged ,Prospective Studies ,MINDACT investigators and the TRANSBIG Consortium ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeMINDACT demonstrated that 46% of patients with early breast cancer at high clinical but low genomic risk on the basis of MammaPrint may safely avoid adjuvant chemotherapy. A second random assignment (R-C) compared docetaxel-capecitabine with an anthracycline-based regimen.Patients and methodsR-C randomly assigned patients 1:1 between standard anthracycline-based regimens, with or without taxanes (control) and experimental docetaxel 75 mg/m2 intravenously plus oral capecitabine 825 mg/m2 two times per day for 14 days (DC) every 3 weeks for 6 cycles. The primary end point was disease-free survival (DFS). Secondary end points included overall survival and safety.ResultsOf 2,832 patients, 1,301 (45%) were randomly assigned, and 97% complied with R-C assignment. In the control arm, 29.6% only received taxanes (0.5% of N0 patients). DFS events (n = 148) were much less than required (n = 422) as a result of a lower-than-expected accrual and event rate. At 5 years of median follow-up, DFS was not different between DC (n = 652) and control (n = 649; 90.7% [95% CI, 88% to 92.8%] v 88.8% [95% CI, 85.9% to 91.1%]; hazard ratio [HR], 0.83 [95% CI, 0.60 to 1.15]; P = .26). Overall survival (HR, 0.91 [95% CI, 0.54 to 1.53]) and DFS in the clinical high and genomic high-risk subgroup (86.1% v 88.1%; HR, 0.83 [95% CI, 0.58 to 1.21]) were similar in both arms. DC led to more grade 1 neuropathy (27.1% v 11.2%) and more grade 2 hand/foot syndrome (28.5% v 3.3%) and diarrhea (13.7% v 5.8%). Serious cardiac events occurred in 9 patients (control, n = 4; DC, n = 5). Fifty-three patients developed second cancers (control, n = 32; DC, n = 21; leukemia: 2 v 1). Five treatment-related deaths occurred (control, 2 [0.3%]; DC, 3 [0.5%]).ConclusionAlthough underpowered, this second randomization in MINDACT did not show any improvement in outcome or safety with the use of DC compared with anthracycline-based chemotherapy.
- Published
- 2020