Long-Term Safety and Real-World Effectiveness of Trastuzumab in Breast Cancer

Overview

Journal J Clin Med

Specialty General Medicine

Date 2019 Feb 21

PMID 30781624

Citations 16

Authors

Marco Mazzotta

Eriseld Krasniqi

Giacomo Barchiesi

Laura Pizzuti

Federica Tomao

Maddalena Barba

Patrizia Vici

Affiliations

Soon will be listed here.

Abstract

Trastuzumab is a milestone in the treatment of human epidermal growth factor receptor 2 positive (HER2+) breast cancer (BC), in both the early and metastatic settings. Over the last two decades, clinical trials have established the good safety profile of trastuzumab. Cardiotoxicity remains the most frequent adverse event, more commonly exemplified by an asymptomatic decline in the left ventricular ejection fraction rather than congestive heart failure. Results from several long-term (>5 years) safety analyses have been recently published, with the inherent evidence substantially confirming the findings from previous trials. The clinical experience gained over the years in the use of trastuzumab has also fueled a number of observational studies focused on the effectiveness of this drug in the real-world settings. We herein reviewed the evidence available from tree major databases, namely, PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL), to explore and critically discuss key issues related to the long-term safety and effectiveness of trastuzumab in clinical practice.

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References

Owens M, Horten B, Da Silva M . HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues. Clin Breast Cancer. 2004; 5(1):63-9. DOI: 10.3816/cbc.2004.n.011. View

Buzdar A, Ibrahim N, Francis D, Booser D, Thomas E, Theriault R . Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel, and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005; 23(16):3676-85. DOI: 10.1200/JCO.2005.07.032. View

Piccart-Gebhart M, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I . Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005; 353(16):1659-72. DOI: 10.1056/NEJMoa052306. View

Romond E, Perez E, Bryant J, Suman V, Geyer Jr C, Davidson N . Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005; 353(16):1673-84. DOI: 10.1056/NEJMoa052122. View

Dawood S, Gonzalez-Angulo A, Peintinger F, Broglio K, Symmans W, Kau S . Efficacy and safety of neoadjuvant trastuzumab combined with paclitaxel and epirubicin: a retrospective review of the M. D. Anderson experience. Cancer. 2007; 110(6):1195-200. DOI: 10.1002/cncr.22895. View

Viani G, Afonso S, Stefano E, De Fendi L, Soares F . Adjuvant trastuzumab in the treatment of her-2-positive early breast cancer: a meta-analysis of published randomized trials. BMC Cancer. 2007; 7:153. PMC: 1959236. DOI: 10.1186/1471-2407-7-153. View

Joensuu H, Bono P, Kataja V, Alanko T, Kokko R, Asola R . Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial. J Clin Oncol. 2009; 27(34):5685-92. DOI: 10.1200/JCO.2008.21.4577. View

Gianni L, Eiermann W, Semiglazov V, Manikhas A, Lluch A, Tjulandin S . Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a.... Lancet. 2010; 375(9712):377-84. DOI: 10.1016/S0140-6736(09)61964-4. View

Jo Chien A, Rugo H . The cardiac safety of trastuzumab in the treatment of breast cancer. Expert Opin Drug Saf. 2010; 9(2):335-46. DOI: 10.1517/14740331003627441. View

10.

Untch M, Rezai M, Loibl S, Fasching P, Huober J, Tesch H . Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010; 28(12):2024-31. DOI: 10.1200/JCO.2009.23.8451. View

11.

Russell S, Blackwell K, Lawrence J, Pippen Jr J, Roe M, Wood F . Independent adjudication of symptomatic heart failure with the use of doxorubicin and cyclophosphamide followed by trastuzumab adjuvant therapy: a combined review of cardiac data from the National Surgical Adjuvant breast and Bowel Project B-31 and.... J Clin Oncol. 2010; 28(21):3416-21. DOI: 10.1200/JCO.2009.23.6950. View

12.

Untch M, Fasching P, Konecny G, Hasmuller S, Lebeau A, Kreienberg R . Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol. 2011; 29(25):3351-7. DOI: 10.1200/JCO.2010.31.4930. View

13.

Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M . Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011; 365(14):1273-83. PMC: 3268553. DOI: 10.1056/NEJMoa0910383. View

14.

Zeglinski M, Ludke A, Jassal D, Singal P . Trastuzumab-induced cardiac dysfunction: A 'dual-hit'. Exp Clin Cardiol. 2011; 16(3):70-4. PMC: 3209542. View

15.

Kaufman P, Brufsky A, Mayer M, Rugo H, Tripathy D, Yood M . Treatment patterns and clinical outcomes in elderly patients with HER2-positive metastatic breast cancer from the registHER observational study. Breast Cancer Res Treat. 2012; 135(3):875-83. PMC: 3439611. DOI: 10.1007/s10549-012-2209-z. View

16.

Romond E, Jeong J, Rastogi P, Swain S, Geyer Jr C, Ewer M . Seven-year follow-up assessment of cardiac function in NSABP B-31, a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel (ACP) with ACP plus trastuzumab as adjuvant therapy for patients with node-positive, human.... J Clin Oncol. 2012; 30(31):3792-9. PMC: 3478574. DOI: 10.1200/JCO.2011.40.0010. View

17.

Natoli C, Vici P, Sperduti I, Grassadonia A, Bisagni G, Tinari N . Effectiveness of neoadjuvant trastuzumab and chemotherapy in HER2-overexpressing breast cancer. J Cancer Res Clin Oncol. 2013; 139(7):1229-40. PMC: 3678021. DOI: 10.1007/s00432-013-1436-y. View

18.

Tripathy D, Kaufman P, Brufsky A, Mayer M, Yood M, Yoo B . First-line treatment patterns and clinical outcomes in patients with HER2-positive and hormone receptor-positive metastatic breast cancer from registHER. Oncologist. 2013; 18(5):501-10. PMC: 3662840. DOI: 10.1634/theoncologist.2012-0414. View

19.

Takada M, Ishiguro H, NAGAI S, Ohtani S, Kawabata H, Yanagita Y . Survival of HER2-positive primary breast cancer patients treated by neoadjuvant chemotherapy plus trastuzumab: a multicenter retrospective observational study (JBCRG-C03 study). Breast Cancer Res Treat. 2014; 145(1):143-53. DOI: 10.1007/s10549-014-2907-9. View

20.

de Azambuja E, Procter M, Van Veldhuisen D, Agbor-Tarh D, Metzger-Filho O, Steinseifer J . Trastuzumab-associated cardiac events at 8 years of median follow-up in the Herceptin Adjuvant trial (BIG 1-01). J Clin Oncol. 2014; 32(20):2159-65. DOI: 10.1200/JCO.2013.53.9288. View