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trastuzumab (Herceptin, Herzuma, CT-P6)

Indications: - HER2 overexpressing breast cancer [6,21] (used in addition to adjuvant chemotherapy) - HER2-positive gastric carcinoma (used in addition to chemotherapy) [17] Dosage: 1) 8 mg/kg IV infusion over 90 minutes (1st dose) 2) subsequent doses 6 mg/kg, every 3 weeks for 1 year [3] a) may be given for 9 weeks rather than 1 year [4] b) no reason to change 1 year duration of therapy [8] c) 6 months of therapy equivalent to 1 year [19] Monitor: - assess left ventricular function prior to treatment [7] - monitor cardiac function with echocardiography during & after treatment* [7] * no indication for continued surveillance with echocardiography or cardiac magnetic resonance imaging if LV systolic function normal 6 months after completion of therapy, & no signs or symptoms of heart failure [7] Adverse effects: - infusion reaction - cardiotoxicity*, congestive heart failure, cardiomyopathy* (1%) [2] - reversible LV systolic dysfunction [7] - risk 27% if treated concurrently with trastuzumab + anthracycline, 13% with trastuzumab * paclitaxel, 5% with trastuzumab alone [20] - risk may be higher in practice than reported in clinical trials (RR=1.8) [9] - effects largely reversible [7] - not dose-dependent [7] - unlikely to occur one year after the end of trastuzumab therapy [20] * cardiotoxicity may be diminished if given before anthracycline * restrictive cardiomyopathy not confirmed as complication Mechanism of action: 1) monoclonal antibody against erbB2 (her2/neu) receptor tyrosine kinase 2) reduces risk of breast cancer recurrence, 2nd primary cancer & mortality [3] Notes: - Manufacturer: Genentech Inc - distinguish from ado-trastuzumab emtansine (Kadcyla) with different dosage & treatment schedules [10] - biosimilar (CT-P6) equally effective [18] - cost: $80,000/year (2018) [19]

Interactions

drug adverse effects of pharmaceutical monoclonal antibodies

Specific

ado-trastuzumab emtansine (Kadcyla, T-DM1) fam-trastuzumab deruxtecan-nxki (Enhertu)

General

antineoplastic monoclonal antibody

References

  1. Herceptin (Trastuzumab): Questions and Answers http://cis.nci.nih.gov/fact/7_45.htm
  2. http://www.fda.gov/medwatch/safety/2005/safety05.htm#Herceptin
  3. Piccart-Gebhart MJ et al, Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer N Engl J Med 2005 Oct 20;352:1659-72 PMID: 16236737 - Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84. PMID: 16236738 - Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, Gianni L, Baselga J, Bell R, Jackisch C, Cameron D, Dowsett M, Barrios CH, Steger G, Huang CS, Andersson M, Inbar M, Lichinitser M, Lang I, Nitz U, Iwata H, Thomssen C, Lohrisch C, Suter TM, Ruschoff J, Suto T, Greatorex V, Ward C, Straehle C, McFadden E, Dolci MS, Gelber RD; Herceptin Adjuvant (HERA) Trial Study Team. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1659-72. PMID: 16236737 - Hortobagyi GN. Trastuzumab in the treatment of breast cancer. N Engl J Med. 2005 Oct 20;353(16):1734-6. No abstract available. PMID: 16236745
  4. Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, Utriainen T, Kokko R, Hemminki A, Tarkkanen M, Turpeenniemi-Hujanen T, Jyrkkio S, Flander M, Helle L, Ingalsuo S, Johansson K, Jaaskelainen AS, Pajunen M, Rauhala M, Kaleva-Kerola J, Salminen T, Leinonen M, Elomaa I, Isola J; FinHer Study Investigators. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006 Feb 23;354(8):809-20. PMID: 16495393
  5. Guarneri V et al, Long-term cardiac tolerability of trastuzumab in metastatic breast cancer. The M.D. Andersion Cancer Center experience. J Clin Oncol 2006, 24:4107 PMID: 16908934
  6. Smith I et al, 2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: A randomized controlled trial. Lancet 2007, 369:29 PMID: 17208639
  7. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17. 18, 19. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018, 2022.
  8. PHARE trial results comparing 6 to 12 months of adjuvant trastuzumab in early breast cancer EMSO: Vienna 2012 Congress European Society for Medical Oncology http://www.esmo.org/events/vienna-2012-congress/congress-news/view.html?tx_ttnews[tt_news]=1673 - Updated results of HERA study: Extending trastuzumab for 2 years does not improve outcomes versus 1-year treatment. EMSO: Vienna 2012 Congress European Society for Medical Oncology http://www.esmo.org/events/vienna-2012-congress/congress-news/view.html?tx_ttnews[pointer]=1&tx_ttnews[tt_news]=1672
  9. Chen J et al. Incidence of heart failure or cardiomyopathy after adjuvant trastuzumab therapy for breast cancer. J Am Coll Cardiol 2012 Dec 18; 60:2504. PMID: 23158536 - Lenihan DJ. Progression of heart failure from AHA/ACC stage A to stage B or even C: Can we all agree we should try to prevent this from happening? J Am Coll Cardiol 2012 Dec 18; 60:2513. PMID: 23158534
  10. FDA MedWarch. May 6, 2013 Kadcyla (ado-trastuzumab emtansine): Drug Safety Communication - Potential Medication Errors Resulting from Name Confusion. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm350817.htm
  11. Dahabreh IJ, Linardou H, Siannis F et al Trastuzumab in the adjuvant treatment of early-stage breast cancer: a systematic review and meta-analysis of randomized controlled trials. Oncologist. 2008 Jun;13(6):620-30 PMID: 18586917
  12. Ewer MS, Vooletich MT, Durand JB et al Reversibility of trastuzumab-related cardiotoxicity: new insights based on clinical course and response to medical treatment. J Clin Oncol. 2005 Nov 1;23(31):7820-6. PMID: 16258084
  13. Deprecated Reference
  14. Fiuza M Cardiotoxicity associated with trastuzumab treatment of HER2+ breast cancer. Adv Ther. 2009 Jul;26 Suppl 1:S9-17 PMID: 19669637
  15. Perez EA, Suman VJ, Davidson NE et al Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. J Clin Oncol. 2008 Mar 10;26(8):1231-8 PMID: 18250349
  16. Slamon D, Eiermann W, Robert N et al Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83 PMID: 21991949
  17. Bang YJ, Van Cutsem E, Feyereislova A et al Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro- oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97 PMID: 20728210
  18. Stebbing J, Baranau Y, Baryash V et al CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial. The Lancet Oncology. June 4, 2017 PMID: 28592386 http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30434-5/fulltext?elsca1=tlpr
  19. Bankhead C Six Months of Trastuzumab Equal to 12 in Breast Ca - Similar outcomes and less cardiotoxicity, but more research needed. MedPage Today. May 16, 2018 https://www.medpagetoday.com/meetingcoverage/asco/72917 - Earl HM, et al PERSEPHONE: 6 versus 12 months (m) of adjuvant trastuzumab in patients (pts) with HER2 positive (+) early breast cancer (EBC): Randomised phase 3 non-inferiority trial with definitive 4-year (yr) disease-free survival (DFS) results. American Society of Clinical Oncology (ASCO) 2018; Abstract 506 - Elia J, Sofair A, Chavey WE Herceptin Study Suggests a Shorter, 6-Month Course for Breast Cancer Will Work. Physician's First Watch, May 18, 2018 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
  20. Hudis CA. Trastuzumab--mechanism of action and use in clinical practice. N Engl J Med 2007 Jul 6; 357:39 PMID: 17611206 https://www.nejm.org/doi/full/10.1056/NEJMra043186
  21. Davenport L Astonishing' PFS Improvement in Metastatic HER+ Breast Cancer. Medscape. September 22, 2021 https://www.medscape.com/viewarticle/959223
  22. HIGHLIGHTS OF PRESCRIBING INFORMATION HERZUMA (trastuzumab-pkrb) for injection, for intravenous use Initial U.S. Approval: 2018 biosimilar* to HERCEPTIN (trastuzumab). https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761091s000lbl.pdf

Component-of

hyaluronidase/trastuzumab hylenex/pertuzumab/trastuzumab pertuzumab/trastuzumab with hyaluronidase (Phesgo)