Raadpleeg ook literatuurlijst specifiek bij borstkanker van arts-bioloog drs. Engelbert Valstar

9 december 2018: Bron: SABCS 2018

Het toedienen van trastuzumab / emtansine i.p.v. trastuzumab (herceptin) bij patiënten met niet volledige operabele borstkanker HER2 pos.  volgend op standaard vooraf op taxaan gebaseerde chemotherapie verbetert de resultaten aanzienlijk. Op drie jaars meting waren 11 procent meer patienten ziektevrij dan bij alleen herceptin (77 vs 88 procent). Dit blijkt uit de resultaten van de fase III studie (KATHERINE) en werd gepresenteerd op het San Antonio Breast Cancer Symposium in 2018 van afgelopen week.

T-DM1


In deze KATHERINE studie werden patiënten met officieel bevestigde HER2 + primaire borstkanker opgenomen die vooraf aan een operatie chemotherapie plus op de HER2-gerichte therapie kregen (chemokuur was op taxaanbasis en bevatte ook trastuzumab, gevolgd door een operatie). Alle patiënten hadden resterend tumorweefsel of in lymfklieren van oksel of borstgebied na de operatie. . Binnen 12 weken na de operatie werden de patiënten gerandomiseerd ingedeeld 1: 1 voor trastuzumab / emtansine (3,6 mg / kg) of trastuzumab (6 mg / kg) intraveneus elke 3 weken gedurende 14 cycli.

Het primaire doel was invasieve ziektevrije overleving (IDFS). Er was een statistisch significante verbetering op 3-jaars meting van IDFS van 11,3%: 77% met trastuzumab versus 88,3% met trastuzumab / emtansine (hazard ratio 0,50, 95% betrouwbaarheidsinterval 0,39-0,64, p <.0001).

Secundaire doelen waren ziektevrije overleving en recidieven op afstand. Beide waren ook verminderd in de trastuzumab / emtansine-arm, aldus studieleider Dr. Geyer.
Bijwerkingen van trastuzumab / emtansine-therapie waren zoals verwacht en werden over het algemeen goed verdragen en behandeld. De meerderheid van de bijwerkingenwas graad 1 of 2 en omvatte vermoeidheid, misselijkheid, hoofdpijn, gevoelloosheid van ledematen en obstipatie.

Hier een tabel van de resultaten:

Kaplan–Meier Estimates of Survival in the Interim Analysis.

The early reporting efficacy boundary was crossed at the prespecified interim analysis, which triggered full trial

Het volledige studierapport: Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer is gratis in te zien.

Heir het abstract van de studie:

Substituting the antibody-drug conjugate trastuzumab/emtansine for trastuzumab in patients with residual breast cancer disease following standard neoadjuvant taxane-based chemotherapy improves outcomes considerably

Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer

  • Gunter von Minckwitz, M.D.,
  • Chiun-Sheng Huang, M.D., Ph.D.,
  • Max S. Mano, M.D., Ph.D.,
  • Sibylle Loibl, M.D.,
  • Eleftherios P. Mamounas, M.D.,
  • Michael Untch, M.D., Ph.D.,
  • Norman Wolmark, M.D.,
  • Priya Rastogi, M.D.,
  • Andreas Schneeweiss, M.D.,
  • Andres Redondo, M.D., Ph.D.,
  • Hans H. Fischer, M.D.,
  • William Jacot, M.D., Ph.D.,
  • Alison K. Conlin, M.D.,
  • Claudia Arce-Salinas, M.D., Ph.D.,
  • Irene L. Wapnir, M.D.,
  • Christian Jackisch, M.D., Ph.D.,
  • Michael P. DiGiovanna, M.D., Ph.D.,
  • Peter A. Fasching, M.D.,
  • John P. Crown, M.D.,
  • Pia Wülfing, M.D.,
  • Zhimin Shao, M.D.,
  • Elena Rota Caremoli, M.D.,
  • Haiyan Wu, Ph.D.,
  • Lisa H. Lam, Pharm.D.,
  • David Tesarowski, Ph.D.,
  • Melanie Smitt, M.D.,
  • Hannah Douthwaite, M.Sc.,
  • Stina M. Singel, M.D., Ph.D.,
  • and Charles E. Geyer, Jr., M.D.
  • for the KATHERINE Investigators*

Abstract

Background

Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)–targeted therapy have a worse prognosis than those who have no residual cancer. Trastuzumab emtansine (T-DM1), an antibody–drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy.

Methods

We conducted a phase 3, open-label trial involving patients with HER2-positive early breast cancer who were found to have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab. Patients were randomly assigned to receive adjuvant T-DM1 or trastuzumab for 14 cycles. The primary end point was invasive disease–free survival (defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause).

Results

At the interim analysis, among 1486 randomly assigned patients (743 in the T-DM1 group and 743 in the trastuzumab group), invasive disease or death had occurred in 91 patients in the T-DM1 group (12.2%) and 165 patients in the trastuzumab group (22.2%). The estimated percentage of patients who were free of invasive disease at 3 years was 88.3% in the T-DM1 group and 77.0% in the trastuzumab group. Invasive disease–free survival was significantly higher in the T-DM1 group than in the trastuzumab group (hazard ratio for invasive disease or death, 0.50; 95% confidence interval, 0.39 to 0.64; P<0.001). Distant recurrence as the first invasive-disease event occurred in 10.5% of patients in the T-DM1 group and 15.9% of those in the trastuzumab group. The safety data were consistent with the known safety profile of T-DM1, with more adverse events associated with T-DM1 than with trastuzumab alone.

Conclusions

Among patients with HER2-positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, the risk of recurrence of invasive breast cancer or death was 50% lower with adjuvant T-DM1 than with trastuzumab alone. (Funded by F. Hoffmann–La Roche/Genentech; KATHERINE ClinicalTrials.gov number, NCT01772472.)

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Plaats een reactie ...

1 Reactie op "Trastuzumab/Emtansine geeft nog betere resultaten dan trastuzumab (Herceptin) (88 vs 77 procent ziektevrij op 3-jaars meting) bij resterend tumorweefsel in lymfklieren na chemo en operatie bij HER@ pos. borstkanker"

  • e.valstar :
    De ziektevrije overleving met emtansine erbij is beter, maar dat wil nog niet zeggen dat de sterfte er verder door verlaagd is. Ik zou deze combinatie overigens zeker aanbevelen. Bedenk wel dat juist het herceptin in deze een fantastisch middel is, dat als adjuvans de sterfte al zeer beduidend verlaagt!

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