Long-Term Follow-Up of the E1199 Phase III Trial Evaluating the Role of Taxane and Schedule in Operable Breast Cancer
- PMID: 26077235
- PMCID: PMC4500829
- DOI: 10.1200/JCO.2015.60.9271
Long-Term Follow-Up of the E1199 Phase III Trial Evaluating the Role of Taxane and Schedule in Operable Breast Cancer
Abstract
Purpose: To determine long-term outcomes in a clinical trial evaluating the role of taxane type and schedule in operable breast cancer and evaluate the impact of obesity and black race on outcome.
Patients and methods: A total of 4,954 eligible women with stage II to III breast cancer treated with four cycles of doxorubicin plus cyclophosphamide were randomly assigned to receive paclitaxel or docetaxel every 3 weeks for four doses or weekly for 12 doses using a 2 × 2 factorial design. The primary end point was disease-free survival (DFS). Results are expressed as hazard ratios (HRs) from Cox proportional hazards models. All P values are two sided.
Results: When compared with the standard every-3-week paclitaxel arm, after a median follow-up of 12.1 years, DFS significantly improved and overall survival (OS) marginally improved only for the weekly paclitaxel (HR, 0.84; P = .011 and HR, 0.87; P = .09, respectively) and every-3-week docetaxel arms (HR, 0.79; P = .001 and HR, 0.86; P = .054, respectively). Weekly paclitaxel improved DFS and OS (HR, 0.69; P = .010 and HR, 0.69; P = .019, respectively) in triple-negative breast cancer. For hormone receptor-positive, human epidermal growth factor receptor 2-nonoverexpressing disease, no experimental arm improved OS, and black race and obesity were associated with increased risk of breast cancer recurrence and death.
Conclusion: Improved outcomes initially observed for weekly paclitaxel were qualitatively similar but quantitatively less pronounced with longer follow-up, although exploratory analysis suggested substantial benefit in triple-negative disease. Further research is required to understand why obesity and race influence clinical outcome in hormone receptor-positive disease.
Trial registration: ClinicalTrials.gov NCT00004125.
© 2015 by American Society of Clinical Oncology.
Conflict of interest statement
Authors' disclosures of potential conflicts of interest are found in the article online at
Figures
![Fig 1.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4500829/bin/zlj9991053400001.gif)
![Fig 2.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4500829/bin/zlj9991053400002.gif)
![Fig 3.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4500829/bin/zlj9991053400003.gif)
![Fig 4.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4500829/bin/zlj9991053400004.gif)
![Fig 5.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4500829/bin/zlj9991053400005.gif)
![Fig 6.](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/4500829/bin/zlj9991053400006.gif)
Comment in
-
Optimizing Adjuvant Taxanes in Early Breast Cancer.J Clin Oncol. 2015 Jul 20;33(21):2334-6. doi: 10.1200/JCO.2015.61.9312. Epub 2015 Jun 22. J Clin Oncol. 2015. PMID: 26101243 No abstract available.
Similar articles
-
SWOG S0221: a phase III trial comparing chemotherapy schedules in high-risk early-stage breast cancer.J Clin Oncol. 2015 Jan 1;33(1):58-64. doi: 10.1200/JCO.2014.56.3296. Epub 2014 Nov 24. J Clin Oncol. 2015. PMID: 25422488 Free PMC article. Clinical Trial.
-
Efficacy of dose dense doxorubicin and cyclophosphamide followed by paclitaxel versus conventional dose doxorubicin, cyclophosphamide followed by paclitaxel or docetaxel in patients with node-positive breast cancer.Asian Pac J Cancer Prev. 2015;16(4):1471-7. doi: 10.7314/apjcp.2015.16.4.1471. Asian Pac J Cancer Prev. 2015. PMID: 25743817
-
Concurrent doxorubicin plus docetaxel is not more effective than concurrent doxorubicin plus cyclophosphamide in operable breast cancer with 0 to 3 positive axillary nodes: North American Breast Cancer Intergroup Trial E 2197.J Clin Oncol. 2008 Sep 1;26(25):4092-9. doi: 10.1200/JCO.2008.16.7841. Epub 2008 Aug 4. J Clin Oncol. 2008. PMID: 18678836 Free PMC article. Clinical Trial.
-
Taxanes for breast cancer: an evidence-based review of randomized phase II and phase III trials.Clin Breast Cancer. 2000 Apr;1(1):32-40; discussion 41-2. doi: 10.3816/CBC.2000.n.002. Clin Breast Cancer. 2000. PMID: 11899388 Review.
-
Taxane vs. taxane: is the duel at an end? A commentary on a phase-III trial of doxorubicin and docetaxel versus doxorubicin and paclitaxel in metastatic breast cancer: results of the ERASME 3 study.Breast Cancer Res Treat. 2008 Sep;111(2):203-8. doi: 10.1007/s10549-007-9776-4. Epub 2007 Nov 8. Breast Cancer Res Treat. 2008. PMID: 17990102 Review.
Cited by
-
Paclitaxel therapeutic drug monitoring - International association of therapeutic drug monitoring and clinical toxicology recommendations.Eur J Cancer. 2024 May;202:114024. doi: 10.1016/j.ejca.2024.114024. Epub 2024 Mar 19. Eur J Cancer. 2024. PMID: 38513383 Review.
-
Early-stage triple negative breast cancer: the therapeutic role of immunotherapy and the prognostic value of pathological complete response.Explor Target Antitumor Ther. 2024;5(1):232-250. doi: 10.37349/etat.2024.00215. Epub 2024 Feb 28. Explor Target Antitumor Ther. 2024. PMID: 38464390 Free PMC article. Review.
-
Combination of Osimertinib with Concurrent Chemotherapy and Hormonal Therapy for Synchronous NSCLC, Hormone Receptor-Positive Breast Cancer, and Triple-Negative Breast Cancer: Case Report.Case Rep Oncol. 2023 Oct 11;16(1):1080-1086. doi: 10.1159/000533783. eCollection 2023 Jan-Dec. Case Rep Oncol. 2023. PMID: 37900833 Free PMC article.
-
Enhancing Targeted Therapy in Breast Cancer by Ultrasound-Responsive Nanocarriers.Int J Mol Sci. 2023 Mar 13;24(6):5474. doi: 10.3390/ijms24065474. Int J Mol Sci. 2023. PMID: 36982548 Free PMC article. Review.
-
Current Treatment Landscape for Early Triple-Negative Breast Cancer (TNBC).J Clin Med. 2023 Feb 15;12(4):1524. doi: 10.3390/jcm12041524. J Clin Med. 2023. PMID: 36836059 Free PMC article. Review.
References
-
- Henderson IC, Berry DA, Demetri GD, et al. Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003;21:976–983. - PubMed
-
- Mamounas EP, Bryant J, Lembersky B, et al. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: Results from NSABP B-28. J Clin Oncol. 2005;23:3686–3696. - PubMed
-
- Saphner T, Tormey DC, Gray R. Annual hazard rates of recurrence for breast cancer after primary therapy. J Clin Oncol. 1996;14:2738–2746. - PubMed
Publication types
MeSH terms
Substances
Associated data
Grants and funding
- CA180867/CA/NCI NIH HHS/United States
- CA180795/CA/NCI NIH HHS/United States
- U10 CA180821/CA/NCI NIH HHS/United States
- U10 CA180795/CA/NCI NIH HHS/United States
- UG1 CA233196/CA/NCI NIH HHS/United States
- CA180794/CA/NCI NIH HHS/United States
- U10 CA180864/CA/NCI NIH HHS/United States
- U10 CA180802/CA/NCI NIH HHS/United States
- UG1 CA190140/CA/NCI NIH HHS/United States
- U10 CA021115/CA/NCI NIH HHS/United States
- UG1 CA189859/CA/NCI NIH HHS/United States
- CA180820/CA/NCI NIH HHS/United States
- CA180802/CA/NCI NIH HHS/United States
- CA190140/CA/NCI NIH HHS/United States
- U10 CA180790/CA/NCI NIH HHS/United States
- P30 CA015083/CA/NCI NIH HHS/United States
- U10 CA180820/CA/NCI NIH HHS/United States
- CA180790/CA/NCI NIH HHS/United States
- CA189859/CA/NCI NIH HHS/United States
- CA180888/CA/NCI NIH HHS/United States
- U10 CA180794/CA/NCI NIH HHS/United States
- CA180816/CA/NCI NIH HHS/United States
- CA180844/CA/NCI NIH HHS/United States
- U10 CA180867/CA/NCI NIH HHS/United States
- P30 CA013330/CA/NCI NIH HHS/United States
- CA180864/CA/NCI NIH HHS/United States
- UG1 CA233184/CA/NCI NIH HHS/United States
- CA180821/CA/NCI NIH HHS/United States
- U10 CA180888/CA/NCI NIH HHS/United States
- U10 CA180816/CA/NCI NIH HHS/United States
- U10 CA180844/CA/NCI NIH HHS/United States
LinkOut - more resources
Full Text Sources
Medical
Research Materials