Kadsila (trastuzumab emtanzin, T-DM1): pervyy kon\"yugat antitela i khimiopreparata v lechenii HER2-polozhitel'nogo raka molochnoy zhelezy


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Kadcyla (trastuzumab emtansine, T-DM1) is a conjugate of the targeted monoclonal antibody trastuzumab and the cytotoxic drug DM1 (maytansinoid). The article presents the results of two large randomized phase III trials, EMILIA and TH3RESA, including patients with HER2-positive breast cancer(BC) with progression after treatment with taxanes and trastuzumab. Compared with previous standards of treatment (a combination of lapatinib and capecitabine in the EMILIA trial and research-driven treatment in the TH3RESA trial), the application of Kadcyla led to achievement of significant increase in efficacy (progression-free survival, overall survival, objective response). Combination with a favorable range of safety allowed to consider trastuzumab emtansine as a key drug of choice in the second-line treatment of HER2-positive breast cancer.

Full Text

Restricted Access

References

  1. Junttila T.T., Li G., Parsons K., Phillips G.L., Sliwkowski M.X. Trastuzumab - DM1 (T-DM1) retains all the mechanisms of action of trastuzumab and efficiently inhibits growth of lapatinib insensitive breast cancer. Breast Cancer Res. Treat. 2011;128:347-56.
  2. Verma S., MilesD., Gianni L., Krop I.E., Welslau M., Baselga J., Pegram M., Oh D.Y., Dieras V., Guardino E., Fang L., Lu M.W., Olsen S., Blackwell K.; EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N. Engl. J. Med. 2012;367:1783-91.
  3. Alley S.C., Okeley N.M., Senter P.D. Antibodydrug conjugates: targeted drug delivery for cancer. Curr. Opin. Chem. Biol. 2010; 14(4):529-37.
  4. BeeramM., KropI.E., Burris H.A., GirishSR., YuW., Lu M.W., Holden S.N., Modi S. A phase 1 study of weekly dosing of trastuzumab emtansine (T-DM1) in patients with advanced human epidermal growth factor 2-positive breast cancer. Cancer. 2012;118:5733-40.
  5. Burris H.A. III, Rugo H.S., Vukelja S.J., Vogel C.L., Borson R.A., Limentani S., Tan-Chiu E., Krop I.E., Michaelson R.A, Girish S., Amler L., Zheng M., Chu Y.W., Klencke B., O'Shaughnessy J.A. Phase II study of the antibody drug conjugate trastu-zumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)- positive breast cancer after prior HER2-directed therapy. J. Clin. Oncol. 2011;29:398-405.
  6. Krop I.E., LoRusso P., Miller K.D., Modi S., Yardley D., Rodriguez G., Guardino E., Lu M., Zheng M., Girish S., Amler L., Winer E.P., Rugo H.S. A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. J. Clin. Oncol. 2012;30:3234-41
  7. Hurvitz S.A., Dirix L., Kocsis J., Bianchi G.V., Lu J., Vinholes J., Guardino E., Song C., Tong B., Ng V., Chu Y.W., Perez E.A. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J. Clin. Oncol. 2013; 31:1157-63.
  8. Krop I.E., Kim S.B., Gonzalez-Martin A., LoRusso P.M., Ferrero J.M., Smitt M., Yu R., Leung A.C., Wildiers H. TH3RESA study collaborators. Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:689-99.
  9. Dieras V., Harbeck N., Budd G.T., Greenson J.K, Guardino A.E., Samant M., Chernyukhin N., Smitt M.C., Krop I.E. Trastuzumab Emtansine in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer: An Integrated Safety Analysis. J. Clin. Oncol. 2014; 32:2750-60.
  10. Li С., Agarwal P., Dent S., Goncalves A., Yi J.-H., Strasak A., Green M., Girish S., LoRusso P. Phase 1 study of trastuzumab emtansine in HER2-positive metastatic breast cancer patients with normal or reduced hepatic function. Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium; December 9-13, 2014; San Antonio, TX. Abstract P4-15-09.
  11. KropI.E.,SuterT.M.,DangC.T.,DirixL.,RomieuG., Zamagni C., Citron M.L., Campone M., Xu N., Smitt M., Gianni L. Feasibility and Cardiac Safety of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (neo)Adjuvant Therapy for Human Epidermal Growth Factor Receptor 2-Positive Early-Stage Breast Cancer. J. Clin. Oncol. 2015;33:1136-42.
  12. Swain S.M.,Kim S.B.,Cortes J.,RoJ.,Semiglazov V., Campone M., Ciruelos E., Ferrero J.M., Schneeweiss A., Knott A., Clark E., Ross G., Benyunes M.C., Baselga J. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, doubleblind, placebo-controlled, phase 3 study. Lancet Oncol. 2013;14:461-71.
  13. Miller K.D., Dieras V., Harbeck N., Andre F., Mahtani R.L., Gianni L., Albain K.S., Crivellari D., Fang L., Michelson G., de Haas S.L., Burris H.A. Phase IIa Trial of Trastuzumab Emtansine With Pertuzumab for Patients With Human Epidermal Growth Factor Receptor 2-Positive, Locally Advanced, or Metastatic Breast Cancer. J. Clin. Oncol. 2014;32:1437-44.
  14. Phillips G.D., Fields C.T., Li G., Dowbenko D., Schaefer G., Miller K., Andre F., Burris H.A. 3rd, Albain K.S., Harbeck N., Dieras V., Crivellari D., Fang L., Guardino E., Olsen S.R., Crocker L.M., Sliwkowski M.X. Dual Targeting of HER2-Positive Cancer with Trastuzumab Emtansine and Pertuzumab: Critical Role for Neuregulin Blockade in Antitumor Response to Combination Therapy. Clin. Cancer Res. 2014;20:456-68.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2015 Bionika Media

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies