Long term continuous Trastuzumab use for HER2-positive advanced breast cancer
AbstractObjectives: Trastuzumab is the standard of care for locally advanced / metastatic her2-positive breast cancer. However, most of these patients will progress within 12 months of trastuzumab therapy. In contrast, there is a paucity of data available on the long-term treatment of patients with Trastuzumab. Our study was conducted to report efficacy and safety data for patients with locally recurrent / metastatic her2-positive breast cancer who received long-term therapy with Trastuzumab (≥5 years).
Methods: This study was a prospective single-arm study of continuous Trastuzumab in patients who were histologically her2-positive and radiologically confirmed inoperable locally recurrent or metastatic breast cancer after complete one year of Trastuzumab plus chemotherapy (in hormone negative/hormone resistance) treatment then continuous Trastuzumab alone , or with hormone therapy (in sensitive hormone positive) without progression [complete or partial response or stable disease]. A total of 50 inoperable local recurrent and metastatic breast cancer patients were treated with continuous intravenous Trastuzumab therapy administered according to the standard Trastuzumab every 3-weeks (8 mg/kg loading dose followed by 3-weekly 6 mg/kg maintenance doses starting 3 weeks after the loading dose) schedule, from January 2014 to January 2019 at the Najaf Cancer Clinic (NCC).
Results: All 50 patients were evaluated with CR occur only in 20% (10/50) with an OAR of 50% (25/50). The cardiac status of these patients remained stable over time for the majority of patients with no marked changes in LVEF%. No treatment-related death was observed. The median OS and median PFS is 61 months and 20 months, respectively.
Conclusion: In her2-positive recurrent and metastatic breast cancer patients, who initially respond to palliative treatment with trastuzumab, continuous trastuzumab can achieve a long-term tumor remission of several years and had significantly improved survival with tolerated and acceptable adverse events.
2. U.S. Breast Cancer Statistics.(2019).[Available online at:https://www.breastcancer.org/symptoms/understand_bc/statistics.Final.pdf,cited 25 December 2019].
3. Mastro LD, Lambertini M, Bighin C, et al. Trastuzumab as first-line therapy in her2-positive metastatic breast cancer patients. Expert Rev Anticancer Ther 2012;12:1391–405.
4. Balasubramaniam T. Proposal for the Inclusion of Trastuzumab in the WHO Model List of Essential Medicines for the Treatment of HER2-Positive Breast Cancer. Geneva, Switzerland: Knowledge Ecology International; 2013. [Available online at: http:// www.who.int/selection_medicines/committees/expert/19/applications/Trastuzumab2_8_2_A_Ad_Final.pdf; cited 4 March 2015].
5. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365(9472):1687–1717.
6. Slamon DJ, Godolphin W, Jones LA, et al. Studies of the her-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989;244:707–12.
7. Baselga J, Cortés J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 2012;366:109–19.
8. Gobbini E, Ezzalfani M, Dieras V, Delaloge S et al (2018) Time trends of overall survival among metastatic breast cancer patients in the real-life ESME cohort. Eur J Cancer 96:17–24.
9. Dawood S, Broglio K, Buzdar AU, Hortobagyi GN, Giordano SH. Prognosis of women with metastatic breast cancer by her2 status and trastuzumab treatment: an institutionalbased review. J Clin Oncol 2010;28:92–8.
10. National Comprehensive Cancer Network: NCCN clinical practice guidelines in oncology (NCCN guidelines®): Breast Cancer, V1. 2017. Available at: http://www.nccn.org/professionals/physician_gls/pdf/breast. pdf. Accessed 04 Dec 2017.
11. Swain SM, Baselga J, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast Cancer. N Engl J Med 2015;372:724–34.
12. Witzel I, Muller V, Abenhardt W, et al. Long-term tumor remission under trastuzumab treatment for her2 positive metastatic breast cancer—results from the her-os patient registry. BMC Cancer 2014;14:806.
13. von Minckwitz G, du Bois A, Schmidt M, et al. Trastuzumab beyond progression in human epidermal growth factor receptor 2-positive advanced breast Cancer: a german breast group 26/breast international group 03-05 study. J Clin Oncol 2009;27:1999–2006.
14. Witzel I, Müller V, Abenhardt W, et al. Long-term tumor remission under trastuzumab treatment for HER2 positive metastatic breast cancer—results from the HER-OS patient registry. BMC Cancer 2014;14:806.
15. Cardoso F (2018) 4th ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4). Ann Oncol 29(8):1634–1657.
16. Giordano SH, Temin S, Chandarlapaty S, Crews JR, Esteva FJ, Kirshner JJ, Krop IE, Levinson J, Lin NU, Modi S, Patt DA, Perlmutter J, Ramakrishna N, Winer EP, Davidson NE (2018) Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: ASCO clinical practice guideline update. J Clin Oncol 36(26):2736–2740.
17. Tripathy D, Slamon DJ, Cobleigh M, et al. Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression. J Clin Oncol 2004;22:1063–70.
18. Viel E, Arbion F, Barbe C, et al. Prolonged complete response after treatment withdrawal in HER2-overexpressed, hormone receptor negative breast cancer with liver metastases: the prospect of disappearance of an incurable disease. BMC Cancer 2014;14:690.
19. Wolff C, Hammond ME et al (2013) Recommendations for human epidermal growth factor receptor 2 testing in breast cancer:American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update. J Clin Oncol 31(31):3997–4013.
20. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J . New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). European journal of cancer. 2009 Jan 1;45(2):228-47.
21. National Comprehensive Cancer Network: NCCN clinical practice guidelines in oncology (NCCN guidelines®): Breast Cancer, V1. 2017.Available at: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed 04 Dec 2017.
22. Daniels B, Kiely BE, Lord SJ, Houssami N, Lu CY, Ward RL, Pearson SA (2018) Long-term survival in trastuzumab-treated patients with HER2-positive metastatic breast cancer: realworld outcomes and treatment: patterns in a whole-of-population Australian cohort (2001–2016). Breast Cancer Res Treat 171(1):151–159.
23. Niikura N, Shimomura A, Fukatsu Y et al (2018) Durable complete response in HER2-positive breast cancer: a multicenter retrospective analysis. Breast Cancer Res Treat 167:81–87.
24. Cardoso F (2018) 4th ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4). Ann Oncol 29(8):1634–1657.
25. Giordano SH, Temin S, Chandarlapaty S, Crews JR, Esteva FJ, Kirshner JJ, Krop IE, Levinson J, Lin NU, Modi S, Patt DA, Perlmutter J, Ramakrishna N, Winer EP, Davidson NE (2018) Systemic therapy for patients with advanced human epidermal growth factor receptor 2-positive breast cancer: ASCO clinical practice guideline update. J Clin Oncol 36(26):2736–2740.
26. Tripathy D, Slamon DJ, Cobleigh M, et al. Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression. J Clin Oncol 2004;22:1063–70.
27. Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, et al. Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol. 2002;20:1215–21.
28. Smichkoska S, Lazarova E. Long term trastuzumab in metastatic setting of the patients with HER2 positive breast Cancer. Breast Can Curr Res.2016;1:103.
29. Kiely BE, Soon YY, Tattersall MH, Stockler MR: How long have I got? Estimating typical, best-case, and worst-case scenarios for patients starting first-line chemotherapy for metastatic breast cancer: a systematic review of recent randomized trials. J Clin Oncol 2010, 29(4):456–463.
30. Montemurro F, Prat A, Rossi V, et al. Potential biomarkers of long-term benefit from single-agent trastuzumab or lapatinib in her2-positive metastatic breast cancer. Mol Oncol 2014;8:20–6.
31. Yeo B, Kotsori K, Mohammed K, Walsh G, Smith IE. Long-term outcome of her2 positive metastatic breast cancer patients treated with first-line trastuzumab. Breast 2015;24:751–7.
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