Assessment of efficacy of trastuzumab (Herceptin) comprising adjuvant therapy of HER2+ breast cancer patients determined based upon statistical analysis of overall survival (OS) and disease-free survival (PFS)

  • Beata Jagielska Department of Oncology Diagnostics, Cardio-oncology and Palliative Medicine, Maria Sklodowska-Curie Memorial Cancer Centre and the Institute of Oncology, Warsaw, Poland, EU
  • Andrzej Czubek Chamber of Commerce “Polish Medicine”, Warsaw, Poland, European Union
  • Konrad Tałasiewicz Department of Oncology Diagnostics, Cardio-oncology and Palliative Medicine, Maria Sklodowska-Curie Memorial Cancer Centre and the Institute of Oncology, Warsaw, Poland, EU
  • Adam Twarowski Bio-Ethics Committee, Maria Sklodowska-Curie Memorial Cancer Centre and the Institute of Oncology, Warsaw, Poland, EU
  • Piotr Rutkowski Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Centre and the Institute of Oncology, Warsaw, Poland, EU
  • Maciej Krzakowski Department of Lung and Thoracic Tumours, Maria Sklodowska-Curie Memorial Cancer Centre and the Institute of Oncology, Warsaw, Poland, EU
  • Bianka Kathryn Saetre Genomics Laboratories, Phoenix Biomolecular Engineering Foundation, San Francisco, CA, 94119, USA
  • Marek Malecki Genomics Laboratories, Phoenix Biomolecular Engineering Foundation, San Francisco, CA, 94119, USA
DOI: 10.26781/2052-8426-2018-02

Abstract

Introduction: In patients suffering from breast cancer, adjuvant radiation, chemotherapy, or immunotherapy, which immediately follow the surgery as the first line therapy, greatly improve overall (OS) and disease-free survival (DFS). Various regimens of adjuvant therapy for these patients have been tested contingent upon the clinical staging. Inclusion of adjuvant immunotherapy is particularly promising.
Specific aim: The aim of this study was to assess efficacy of trastuzumab(Herceptin) -comprising adjuvant immunotherapy in terms of overall and disease-free survival as compared to other adjuvant therapies.
Patients: All patients were presented with the Patient Bill of Rights and have provided the Patient Informed Consent to participate in this study.Eligible patients include those with primary tumors initially staged at the clinical stages: I-T1c N0, II-T0-2, N0-1,or IIIA-T3 N1, or patients for whom neoadjuvant chemotherapy provides the possibility to remove surgically a tumor at the stage IIIA T0-3 N2. Of 9,058 patients enrolled in the Breast Cancer Treatment Program between 2008 and 2015, 6,832 fulfilled the inclusion criteria.
Statistical Analysis: The effects of clinical and demographic factors on overall survival (OS) and disease-free survival(DFS) were assessed using Cox’s proportional hazards regression models. OS and DFS were evaluated with Kaplan-Meier calculations. The study was meeting the criteria for a controlled, open-access clinical trial.
Results: OS rates for years 1-7 were, respectively, 99.42%, 97.26%, 94.57%, 92.41%, 90.48%, 88.63%, and 88.23%; thus with the 5-year survivalat 90.48%. The corresponding data for DFS were 96.17%, 84.07%, 77.26%, 72.57%, 68.59%, 65.04%, and 63.05%, respectively; thus with the 5-year DFS at 68.59%. Adverse effects, with the exception of cardiac complications, occurred in 1194 (17%), while causing withdrawal of 421 (6%) patients. Most of other adverse events were related to hepatotoxicity 1755 (25%) and fatigue 681 (9.7%).
Conclusion: These results demonstrate the great benefits of inclusion of immunotherapy as the adjuvant component as currently the best overall therapeutic strategy for the patients suffering breast cancers. As this strategy greatly exceeds any other therapeutic options available for practicing oncologists at the present time, it definitely justifies allocation of all needed public resources, while assuring highest quality health service for the patients in Poland.

Keywords

breast cancer, trastuzumab, Herceptin, radiotherapy, chemotherapy, immunotherapy, hormonal therapy, adjuvant therapy, human epidermal growth factor receptor – 2, estrogen receptor, progesterone receptor, overall survival, disease-free survival

References

1. National Registry of Cancer, Poland. Epidemiology. Statistics. Available: http://onkologia.org.pl/
2. Dz.U. 2004 nr 210 poz. 2135 Ustawa z dnia 27 sierpnia 2004 r. o świadczeniach opieki zdrowotnej finansowanych ze środków publicznych (in Polish). Available: http://isap.sejm.gov.pl/DetailsServlet?id=WDU20042102135
3. Polish National Drug Progam. Available: http://www.mz.gov.pl/leki/refundacja/programy-lekowe/
4. Review of the available evidence on Trastuzumab for Inclusion in the WHO Essential Medicines List as an anti-neoplastic agent Union for International Cancer Control Route deFrontenex, 62 1207 Geneva Switzerland Dana-Farber Cancer Institute Center for Global Cancer Medicine 450 Brookline Avenue, Boston, MA 02215.
5. Bonifazi M , Franchi M , Rossi M et al.Long term survival of HER2-positive early breast cancer treated with trastuzumab-based adjuvant regimen: a large cohort study from clinical practice. Breast 2014;23:573-578.
6. Gianni L , Dafni U , Gelber RD et al. Treatment with trastuzumab for 1 year after adjuvant chemotherapy in patients with HER2-positive early breast cancer: a 4-year follow-up of a randomised controlled trial. The Lancet Oncology; Vol. 12,3:236-244.
7. Edith A. Perez, Edward H. Romond, Vera J. Suman et al. Four-Year Follow-Up of Trastuzumab Plus Adjuvant Chemotherapy for Operable Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Joint Analysis of Data From NCCTG N9831 and NSABP B-31. J Clin Oncol. 2014;32(33).
8. Perez E ., Romond E ., Suman V . et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. Br J Cancer. 2012;3;106(1).
9. Webster RM , Abraham J , Palaniappan N et al. Exploring the use and impact of adjuvant trastuzumab for HER2-positive breast cancer patients in a large UK cancer network. Do the results of international clinical trials translate into a similar benefit for patients in South East Wales? Br J cancer 2012;3:106(1):32-8.
10. Dennis S, Wolfgang E, Nicholas R et al. Adjuvant Trastuzumab in HER2-Positive Breast Cancer. N Engl J Med 2011;365:1273-1283.
11. Early Breast Cancer Trialists' Collaborative Group. Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet 1998;352:930-94.
12. Gennari A, Sormani MP, Pronzato P et al. HER2 status and efficacy of adjuvant anthracyclines in early breast cancer: a pooled analysis of randomized trials. J Natl Cancer Inst 2008;100:14-20.
13. Qin Y-Y, Li H, Guo X-J et al. Adjuvant Chemotherapy, with or without Taxanes, in Early or Operable Breast Cancer: A Meta-Analysis of 19 Randomized Trials with 30698 Patients. PLoS ONE 6(11): e26946.
14. Piccart-Gebhart M, Procter M, Leyland-Jones B et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 2005;353:1659-1672.
15. Romond E, Perez E, Bryant J et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 2005;353:1673-1684.
16. Smith I, Procter M, Gelber RD et al. 2-Year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial. Lancet 2007;369:29-36.
17. Tan-Chiu E, Yothers G, Romond E, et al. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol
2005;23:7811-7819.
18. Breast cancer in young women. Nat Rev Clin Oncol. 2012; 26;9(8):460-70.
19. Borg M. Breast-conserving therapy in young women with invasive carcinoma of the breast. Journal of Medical Imaging and Radiation Oncology 2004;48(3):376-382.
20. Assi H. A., Khoury K. E., Dbouk H. et al. Epidemiology and prognosis of breast cancer in young women. Journal of Thoracic Disease, 5 (Suppl 1), S2–S8.
21. Wolff AC, Hammond EH, Hicks DG, Dowsett M, McShane LM, Allison KH. 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. DOI: 10.1200/JCO.2013.50.9984 Journal of Clinical Oncology 31, no. 31 (November 2013) 3997-4013
Published
2018-01-18
How to Cite
JAGIELSKA, Beata et al. Assessment of efficacy of trastuzumab (Herceptin) comprising adjuvant therapy of HER2+ breast cancer patients determined based upon statistical analysis of overall survival (OS) and disease-free survival (PFS). Molecular and Cellular Therapies, [S.l.], v. 6, n. 1, jan. 2018. ISSN 2052-8426. Available at: <http://molcelltherapies.com/article/view/202>. Date accessed: 21 apr. 2018. doi: https://doi.org/10.26781/2052-8426-2018-02.
Article Type
Original Research