| Abstract: |
Purpose Docetaxel and cyclophosphamide (TC) was superior to doxorubicin and cyclophosphamide (AC) in a trial in early breast cancer. However, activity of TC relative to AC regimens with a taxane (TaxAC) is unknown. Methods In a series of three adjuvant trials, women were randomly assigned to TC for six cycles (TC6) or to a standard TaxAC regimen. US Oncology Research (USOR) 06-090 compared TC6 with docetaxel, doxorubicin, and cyclophosphamide (TAC6). National Surgical Adjuvant Breast and Bowel Project (NSABP) B-46-I/USOR 07132 compared TC6, TAC6, or TC6 plus bevacizumab. NSABP B-49 compared TC6 with several standard AC and taxane combination regimens. Before any analysis of individual trials, a joint efficacy analysis of TC versus the TaxAC regimens was planned, with invasive disease-free survival (IDFS) as the primary end point. Patients who received TC6 plus bevacizumab on NSABP B-46-I/USOR 07132 were not included. A hazard ratio (HR) from a stratified Cox model that exceeded 1.18 for TC6 versus TaxAC was predefined as inferiority for TC6. The prespecified interim monitoring plan was to report for futility if the HR was . 1.18 when 334 IDFS events were observed (50% of 668 events required for definitive analysis). Results A total of 2,125 patients were randomly assigned to receive TC6 regimens and 2,117 patients were randomly assigned to receive TaxAC regimens. The median follow-up time was 3.3 years. There were 334 IDFS events, and the HR for TC6 versus TaxAC was 1.202 (95% CI, 0.97 to 1.49), which triggered early reporting for futility. The 4-year IDFS was 88.2% for TC6 and was 90.7% for TaxAC (P = .04). Tests for treatment interaction by protocol, hormone receptor status, and nodal status were negative. Conclusion The TaxAC regimens improved IDFS in patients with high-risk human epidermal growth factor receptor 2–negative breast cancer compared with the TC6 regimen. Copyright © 2017 American Society of Clinical Oncology. All rights reserved. |
| Keywords: |
adult; cancer survival; controlled study; disease-free survival; middle aged; major clinical study; clinical trial; fatigue; bevacizumab; doxorubicin; cancer combination chemotherapy; diarrhea; drug efficacy; gastrointestinal hemorrhage; hypertension; side effect; treatment planning; conference paper; paclitaxel; comparative study; disease free survival; chemotherapy, adjuvant; follow up; follow-up studies; lymph node metastasis; antineoplastic agent; lymphatic metastasis; prospective study; prospective studies; multiple cycle treatment; sensory neuropathy; breast cancer; anemia; mastectomy; mucosa inflammation; randomized controlled trial; vomiting; antineoplastic combined chemotherapy protocols; dehydration; myalgia; epidermal growth factor receptor 2; cyclophosphamide; bone pain; clinical protocol; patient monitoring; pathology; breast neoplasms; docetaxel; abdominal pain; arthralgia; febrile neutropenia; fever; pneumonia; hypoxia; alanine aminotransferase; alkaline phosphatase; aspartate aminotransferase; liver failure; chemistry; early cancer; heart failure; heart infarction; thromboembolism; adjuvant chemotherapy; sepsis; receptor, erbb-2; receptors, estrogen; receptors, progesterone; taxoids; headache; phase 3 clinical trial; taxane derivative; estrogen receptor; progesterone receptor; anthracycline; hormone receptor; lung infection; hand foot syndrome; anthracyclines; wound infection; brain ischemia; lung fibrosis; bilirubin blood level; brain hemorrhage; cholecystitis; carcinoma, intraductal, noninfiltrating; allergic reaction; radiation dermatitis; taxoid; carcinoma, ductal, breast; motor neuropathy; erbb2 protein, human; secondary; acute coronary syndrome; taxane; bridged compound; left ventricular systolic dysfunction; infusion related reaction; time to treatment; noncardiac chest pain; humans; human; female; priority journal; peripheral ischemia; bridged-ring compounds
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