Dose-dense sequential adjuvant chemotherapy in the trastuzumab era: final long-term results of the Hellenic Cooperative Oncology Group Phase III HE10/05 Trial.

Antineoplastic Combined Chemotherapy Protocols / adverse effects Australia Breast Neoplasms Chemotherapy, Adjuvant Cyclophosphamide / adverse effects Disease-Free Survival Epirubicin / adverse effects Female Fluorouracil / adverse effects Humans Paclitaxel / adverse effects Trastuzumab / adverse effects

Journal

British journal of cancer

ISSN: 1532-1827

Titre abrégé: Br J Cancer

Pays: England

ID NLM: 0370635

Informations de publication

Date de publication:
09 2022

Historique:

received: 23 07 2021

accepted: 06 05 2022

revised: 13 12 2021

pubmed: 25 5 2022

medline: 19 8 2022

entrez: 24 5 2022

Statut: ppublish

Résumé

Dose-dense sequential chemotherapy with anthracyclines and taxanes achieved an 18% reduction of recurrence risk in early breast cancer (BC). The optimal chemotherapy schedule and interval between cycles remain under investigation. Overall, 990 patients were randomised to receive either three cycles of epirubicin (E, 110 mg/m At a median follow-up of 13.3 years, 330 disease-free survival (DFS) events (33.3%) were reported. DFS and overall survival (OS) did not differ between patients in the combined B and C arms versus arm A either in the entire cohort (HR = 0.90, P = 0.38 and HR = 0.85, P = 0.20) or among trastuzumab-treated patients (HR = 0.69, P = 0.13 and HR = 0.67, P = 0.13). Thirty-four patients (3.4%) developed secondary neoplasms. Overall, no significant differences in survival were found amongst the studied regimens after a long-term observational period. Australian New Zealand Clinical Trials Registry ACTRN12610000151033.

Sections du résumé

BACKGROUND

METHODS

Overall, 990 patients were randomised to receive either three cycles of epirubicin (E, 110 mg/m

RESULTS

At a median follow-up of 13.3 years, 330 disease-free survival (DFS) events (33.3%) were reported. DFS and overall survival (OS) did not differ between patients in the combined B and C arms versus arm A either in the entire cohort (HR = 0.90, P = 0.38 and HR = 0.85, P = 0.20) or among trastuzumab-treated patients (HR = 0.69, P = 0.13 and HR = 0.67, P = 0.13). Thirty-four patients (3.4%) developed secondary neoplasms.

CONCLUSIONS

Overall, no significant differences in survival were found amongst the studied regimens after a long-term observational period.

TRIAL REGISTRATION

Australian New Zealand Clinical Trials Registry ACTRN12610000151033.

Identifiants

DOI: 10.1038/s41416-022-01846-y PMID: 35610366 PMC: PMC9381581

pubmed: 35610366

doi: 10.1038/s41416-022-01846-y

pii: 10.1038/s41416-022-01846-y

pmc: PMC9381581

doi:

Substances chimiques

Epirubicin 3Z8479ZZ5X

Cyclophosphamide 8N3DW7272P

Trastuzumab P188ANX8CK

Paclitaxel P88XT4IS4D

Fluorouracil U3P01618RT

Banques de données

ANZCTR

['ACTRN12610000151033']

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

695-703

Informations de copyright

Références

Ferlay J, Colombet M, Soerjomataram I, Dyba T, Randi G, Bettio M, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer. 2018;103:356–87.

pubmed: 30100160 doi: 10.1016/j.ejca.2018.07.005

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71:7–33.

pubmed: 33433946 doi: 10.3322/caac.21654

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209–49.

pubmed: 33538338 doi: 10.3322/caac.21660

Fisher B, Brown AM, Dimitrov NV, Poisson R, Redmond C, Margolese RG, et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol. 1990;8:1483–96.

pubmed: 2202791 doi: 10.1200/JCO.1990.8.9.1483

Jones SE, Savin MA, Holmes FA, O’Shaughnessy JA, Blum JL, Vukelja S, et al. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006;24:5381–7.

pubmed: 17135639 doi: 10.1200/JCO.2006.06.5391

Peto R, Davies C, Godwin J, Gray R, Pan HC, Clarke M, et al. Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012;379:432–44.

pubmed: 22152853 doi: 10.1016/S0140-6736(11)61625-5

Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, 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;21:976–83.

pubmed: 12637460 doi: 10.1200/JCO.2003.02.063

Martin M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, et al. Adjuvant docetaxel for node-positive breast cancer. N. Engl J Med. 2005;352:2302–13.

pubmed: 15930421 doi: 10.1056/NEJMoa043681

Mamounas EP, Bryant J, Lembersky B, Fehrenbacher L, Sedlacek SM, Fisher 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;23:3686–96.

pubmed: 15897552 doi: 10.1200/JCO.2005.10.517

Jacquin JP, Jones S, Magné N, Chapelle C, Ellis P, Janni W, et al. Docetaxel-containing adjuvant chemotherapy in patients with early stage breast cancer. Consistency of effect independent of nodal and biomarker status: a meta-analysis of 14 randomized clinical trials. Breast Cancer Res Treat. 2012;134:903–13.

pubmed: 22270929 doi: 10.1007/s10549-011-1933-0

Hryniuk W, Levine MN. Analysis of dose intensity for adjuvant chemotherapy trials in stage II breast cancer. J Clin Oncol. 1986;4:1162–70.

pubmed: 3525765 doi: 10.1200/JCO.1986.4.8.1162

Simon R, Norton L. The Norton-Simon hypothesis: designing more effective and less toxic chemotherapeutic regimens. Nat Clin Pract Oncol. 2006;3:406–7.

pubmed: 16894366 doi: 10.1038/ncponc0560

Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003;21:1431–9.

pubmed: 12668651 doi: 10.1200/JCO.2003.09.081

Möbus V, Jackisch C, Lück HJ, du Bois A, Thomssen C, Kuhn W, et al. Ten-year results of intense dose-dense chemotherapy show superior survival compared with a conventional schedule in high-risk primary breast cancer: final results of AGO phase III iddEPC trial. Ann Oncol: Off J Eur Soc Med Oncol. 2018;29:178–85.

doi: 10.1093/annonc/mdx690

Papakonstantinou A, Matikas A, Bengtsson NO, Malmström P, Hedayati E, Steger G, et al. Efficacy and safety of tailored and dose-dense adjuvant chemotherapy and trastuzumab for resected HER2-positive breast cancer: Results from the phase 3 PANTHER trial. Cancer. 2020;126:1175–82.

pubmed: 31851385 doi: 10.1002/cncr.32653

Del Mastro L, De Placido S, Bruzzi P, De Laurentiis M, Boni C, Cavazzini G, et al. Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial. Lancet. 2015;385:1863–72.

pubmed: 25740286 doi: 10.1016/S0140-6736(14)62048-1

Cameron D, Morden JP, Canney P, Velikova G, Coleman R, Bartlett J, et al. Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer in the randomised UK TACT2 trial (CRUK/05/19): a multicentre, phase 3, open-label, randomised, controlled trial. Lancet Oncol. 2017;18:929–45.

pubmed: 28600210 pmcid: 5489700 doi: 10.1016/S1470-2045(17)30404-7

Venturini M, Del Mastro L, Aitini E, Baldini E, Caroti C, Contu A, et al. Dose-dense adjuvant chemotherapy in early breast cancer patients: results from a randomized trial. J Natl Cancer Inst. 2005;97:1724–33.

pubmed: 16333028 doi: 10.1093/jnci/dji398

Swain SM, Tang G, Geyer CE Jr, Rastogi P, Atkins JN, Donnellan PP, et al. Definitive results of a phase III adjuvant trial comparing three chemotherapy regimens in women with operable, node-positive breast cancer: the NSABP B-38 trial. J Clin Oncol. 2013;31:3197–204.

pubmed: 23940225 pmcid: 3757290 doi: 10.1200/JCO.2012.48.1275

Möbus V, von Minckwitz G, Jackisch C, Lück HJ, Schneeweiss A, Tesch H, et al. Node-positive Study (GAIN): a phase III trial comparing two dose-dense regimens (iddEPC versus ddEC-PwX) in high-risk early breast cancer patients. Ann Oncol. 2017;28:1803–10.

pubmed: 28459941 doi: 10.1093/annonc/mdx203

(EBCTCG) EBCTCG. Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials. Lancet. 2019;393:1440–52.

doi: 10.1016/S0140-6736(18)33137-4

Bonilla L, Ben-Aharon I, Vidal L, Gafter-Gvili A, Leibovici L, Stemmer SM. Dose-dense chemotherapy in nonmetastatic breast cancer: a systematic review and meta-analysis of randomized controlled trials. J Natl Cancer Inst. 2010;102:1845–54.

pubmed: 21098761 pmcid: 3001963 doi: 10.1093/jnci/djq409

Petrelli F, Cabiddu M, Coinu A, Borgonovo K, Ghilardi M, Lonati V, et al. Adjuvant dose-dense chemotherapy in breast cancer: a systematic review and meta-analysis of randomized trials. Breast Cancer Res Treat. 2015;151:251–9.

pubmed: 25917869 doi: 10.1007/s10549-015-3405-4

Buzzoni R, Bonadonna G, Valagussa P, Zambetti M. Adjuvant chemotherapy with doxorubicin plus cyclophosphamide, methotrexate, and fluorouracil in the treatment of resectable breast cancer with more than three positive axillary nodes. J Clin Oncol. 1991;9:2134–40.

pubmed: 1960555 doi: 10.1200/JCO.1991.9.12.2134

Perloff M, Norton L, Korzun AH, Wood WC, Carey RW, Gottlieb A, et al. Postsurgical adjuvant chemotherapy of stage II breast carcinoma with or without crossover to a non-cross-resistant regimen: a Cancer and Leukemia Group B study. J Clin Oncol. 1996;14:1589–98.

pubmed: 8622076 doi: 10.1200/JCO.1996.14.5.1589

Shao N, Wang S, Yao C, Xu X, Zhang Y, Zhang Y, et al. Sequential versus concurrent anthracyclines and taxanes as adjuvant chemotherapy of early breast cancer: a meta-analysis of phase III randomized control trials. Breast. 2012;21:389–93.

pubmed: 22542064 doi: 10.1016/j.breast.2012.03.011

Bonadonna G, Zambetti M, Valagussa P. Sequential or alternating doxorubicin and CMF regimens in breast cancer with more than three positive nodes. Ten-year results. J Am Med Assoc.1995;273:542–7.

doi: 10.1001/jama.1995.03520310040027

Fountzilas G, Skarlos D, Dafni U, Gogas H, Briasoulis E, Pectasides D, et al. Postoperative dose-dense sequential chemotherapy with epirubicin, followed by CMF with or without paclitaxel, in patients with high-risk operable breast cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol. 2005;16:1762–71.

pubmed: 16148021 doi: 10.1093/annonc/mdi366

Gogas H, Dafni U, Karina M, Papadimitriou C, Batistatou A, Bobos M, et al. Postoperative dose-dense sequential versus concomitant administration of epirubicin and paclitaxel in patients with node-positive breast cancer: 5-year results of the Hellenic Cooperative Oncology Group HE 10/00 phase III Trial. Breast Cancer Res Treat. 2012;132:609–19.

pubmed: 22187126 doi: 10.1007/s10549-011-1913-4

Fountzilas G, Dafni U, Gogas H, Linardou H, Kalofonos HP, Briasoulis E, et al. Postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel and CMF in patients with high-risk breast cancer: safety analysis of the Hellenic Cooperative Oncology Group randomized phase III trial HE 10/00. Ann Oncol. 2008;19:853–60.

pubmed: 18042835 doi: 10.1093/annonc/mdm539

Fountzilas G, Dafni U, Papadimitriou C, Timotheadou E, Gogas H, Eleftheraki AG, et al. Dose-dense sequential adjuvant chemotherapy followed, as indicated, by trastuzumab for one year in patients with early breast cancer: first report at 5-year median follow-up of a Hellenic Cooperative Oncology Group randomized phase III trial. BMC Cancer. 2014;14:515.

pubmed: 25026897 pmcid: 4223601 doi: 10.1186/1471-2407-14-515

Goldhirsch A, Glick JH, Gelber RD, Coates AS, Thürlimann B, Senn HJ. Meeting highlights: international expert consensus on the primary therapy of early breast cancer 2005. Ann Oncol. 2005;16:1569–83.

pubmed: 16148022 doi: 10.1093/annonc/mdi326

World Medical Association Declaration of Helsinki. Ethical principles for medical research involving human subjects. Bulletin of the World Health Organization. 2001;79:373–4.

Hudis CA, Barlow WE, Costantino JP, Gray RJ, Pritchard KI, Chapman JA, et al. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol. 2007;25:2127–32.

pubmed: 17513820 doi: 10.1200/JCO.2006.10.3523

Cuzick J. Statistical controversies in clinical research: long-term follow-up of clinical trials in cancer. Ann Oncol. 2015;26:2363–6.

pubmed: 26433395 pmcid: 4658544 doi: 10.1093/annonc/mdv392

Darby SC, Ewertz M, McGale P, Bennet AM, Blom-Goldman U, Brønnum D, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N. Engl J Med. 2013;368:987–98.

pubmed: 23484825 doi: 10.1056/NEJMoa1209825

van Leeuwen FE, Benraadt J, Coebergh JW, Kiemeney LA, Gimbrère CH, Otter R, et al. Risk of endometrial cancer after tamoxifen treatment of breast cancer. Lancet. 1994;343:448–52.

pubmed: 7905955 doi: 10.1016/S0140-6736(94)92692-1

Early Breast Cancer Trialists' Collaborative Group. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–717.

Jones SE, Erban J, Overmoyer B, Budd GT, Hutchins L, Lower E, et al. Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol. 2005;23:5542–51.

pubmed: 16110015 doi: 10.1200/JCO.2005.02.027

Sparano JA, Zhao F, Martino S, Ligibel JA, Perez EA, Saphner T, et al. Long-Term follow-up of the E1199 Phase III trial evaluating the role of taxane and schedule in operable breast cancer. J Clin Oncol. 2015;33:2353–60.

pubmed: 26077235 pmcid: 4500829 doi: 10.1200/JCO.2015.60.9271

Lambertini M, Poggio F, Bruzzone M, Conte B, Bighin C, de Azambuja E, et al. Dose-dense adjuvant chemotherapy in HER2-positive early breast cancer patients before and after the introduction of trastuzumab: exploratory analysis of the GIM2 trial. Int J Cancer. 2020;147:160–9.

pubmed: 31724170 doi: 10.1002/ijc.32789

Del Mastro L, Bruzzi P, Nicolò G, Cavazzini G, Contu A, D’Amico M, et al. HER2 expression and efficacy of dose-dense anthracycline-containing adjuvant chemotherapy in breast cancer patients. Br J Cancer. 2005;93:7–14.

pubmed: 15970926 pmcid: 2361477 doi: 10.1038/sj.bjc.6602660

Foukakis T, Papakonstantinou A, Matikas A, Bengtsson N-O, Malmström P, Hedayati E, et al. Tailored dose-dense chemotherapy in combination with trastuzumab as adjuvant therapy for HER2-positive breast cancer: a secondary analysis of the phase III PANTHER trial. J Clin Oncol. 2019;37:553.

doi: 10.1200/JCO.2019.37.15_suppl.553

Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, et al. 11 years’ follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017;389:1195–205.

pubmed: 28215665 pmcid: 5465633 doi: 10.1016/S0140-6736(16)32616-2

Dong C, Chen L. Second malignancies after breast cancer: the impact of adjuvant therapy. Mol Clin Oncol. 2014;2:331–6.

pubmed: 24772296 pmcid: 3999127 doi: 10.3892/mco.2014.250

Abu-Khalaf MM, Juneja V, Chung GG, DiGiovanna MP, Sipples R, McGurk M, et al. Long-term assessment of cardiac function after dose-dense and -intense sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) as adjuvant therapy for high risk breast cancer. Breast Cancer Res Treat. 2007;104:341–9.

pubmed: 17051423 doi: 10.1007/s10549-006-9413-7

Dent SF, Botros J, Rushton M, Aseyev O, Levine MN, Parulekar WR, et al. Anthracycline-induced cardiotoxicity in patients with early-stage breast cancer: the Canadian Cancer Trials Group (CCTG) MA.21 experience. Breast Cancer Res Treat. 2020;184:733–41.

pubmed: 32940847 doi: 10.1007/s10549-020-05887-w