Doxorubicin Hydrochloride, Cyclophosphamide, and Paclitaxel With or Without Bevacizumab in Treating Patients With Lymph Node-Positive or High-Risk, Lymph Node-Negative Breast Cancer
Summary
This randomized phase III trial studies doxorubicin hydrochloride, cyclophosphamide, and paclitaxel to see how well they work with or without bevacizumab in treating patients with cancer that has spread to the lymph nodes (lymph node-positive) or cancer that has not spread to the lymph nodes but is at high risk for returning (high-risk, lymph node-negative breast cancer). Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving chemotherapy after surgery may kill any tumor cells that remain after surgery and help prevent the tumor from returning. It is not yet known whether doxorubicin hydrochloride, cyclophosphamide, and paclitaxel are more effective with or without bevacizumab.
Timeline
- Start
- 2007-11-02
- Primary completion
- 2014-01-07
- Completion
- 2027-02-20
Outcome
Missed primary endpoint
registry Arm A (Chemo + Placebo) vs Arm C (Chemo + Bevacizumab Then Bevacizumab Monotherapy); p = 0.17 NCT00433511 ↗
paper Conclusion Incorporation of bevacizumab into sequential anthracycline- and taxane-containing adjuvant therapy does not improve IDFS or overall survival PMID 30040523 ↗
Publications
- Rosenberg SM, O'Neill A, Sepucha K, Miller KD, Dang CT, Northfelt DW, Sledge GW, Schneider BP, Partridge AH. Quality of Life Following Receipt of Adjuvant Chemotherapy With and Without Bevacizumab in Patients With Lymph Node-Positive and High-Risk Lymph Node-Negative Breast Cancer. JAMA Netw Open. 2022 Feb 1;5(2):e220254. doi: 10.1001/jamanetworkopen.2022.0254.
- Ip EH, Saldana S, Miller KD, Carlos RC, Gareen IF, Sparano JA, Graham N, Zhao F, Lee JW, O'Connell NS, Cella D, Peipert JD, Gray RJ, Wagner LI. Tolerability of bevacizumab and chemotherapy in a phase 3 clinical trial with human epidermal growth factor receptor 2-negative breast cancer: A trajectory analysis of adverse events. Cancer. 2021 Dec 15;127(24):4546-4556. doi: 10.1002/cncr.33992. Epub 2021 Nov 2.
- Sparano J, O'Neill A, Alpaugh K, Wolff AC, Northfelt DW, Dang CT, Sledge GW, Miller KD. Association of Circulating Tumor Cells With Late Recurrence of Estrogen Receptor-Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Oncol. 2018 Dec 1;4(12):1700-1706. doi: 10.1001/jamaoncol.2018.2574.
- Miller KD, O'Neill A, Gradishar W, Hobday TJ, Goldstein LJ, Mayer IA, Bloom S, Brufsky AM, Tevaarwerk AJ, Sparano JA, Le-Lindqwister NA, Hendricks CB, Northfelt DW, Dang CT, Sledge GW Jr. Double-Blind Phase III Trial of Adjuvant Chemotherapy With and Without Bevacizumab in Patients With Lymph Node-Positive and High-Risk Lymph Node-Negative Breast Cancer (E5103). J Clin Oncol. 2018 Sep 1;36(25):2621-2629. doi: 10.1200/JCO.2018.79.2028. Epub 2018 Jul 24.
- Partridge AH, Sepucha K, O'Neill A, Miller KD, Baker E, Dang CT, Northfelt DW, Sledge GW, Schneider BP. Does biomarker information impact breast cancer patients' preferences and physician recommendation for adjuvant chemotherapy? Breast Cancer Res Treat. 2017 Oct;165(3):545-553. doi: 10.1007/s10549-017-4338-x. Epub 2017 Jun 23.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Bevacizumab | Monoclonal antibody | — | Intravenous |
| Background | Cyclophosphamide | Other / unclassified | — | Intravenous |
| Background | Doxorubicin | Other / unclassified | — | Intravenous |
| Background | Paclitaxel | Small molecule | — | Intravenous |