7 oktober 2011: bron: N Engl J Med 2011; 365:1273-1283

Een grote gerandomiseerde fase III studie heeft uitgewezen dat het niet perse noodzakelijk is om naast herceptin - trastuzumab ook de zogeheten antracycline chemo te gebruiken die vaak ernstige bijwerkingen geeft. Ook chemo niet gebaseerd op antracycline geeft naast herceptin - trastuzumab een significant verschil in ziektevrije tijd, 5-jaars overleving en overall overleving. Daarmee worden de risico's van hartfalen en kans op leukemie door de chemo vermeden. De resultaten uit de studie waren deze:

Resultaten

Na een gemiddelde follow-up van 65 maanden, 656 patienten konden worden geevalueerd volgens het studieprotocol. De cijfers van de ziektevrije tijd na 5 jaar waren 75% onder de patienten die alleen een antracycline chemo gebruikten (AC-T), 84% bij de groep die AC-T plus herceptin - trastuzumab gebruikten, en 81% die herceptin plus een chemo niet gebaseerd op antracylcine gebruikten ( TCH). De cijfers van de overall overfleving waren resp. 87%, 92%, en 91%. Er was geen significant verschil in effectiviteit tussen de twee groepen die herceptin - trastuzumab kregen. Beide groepen met herceptin waren wel superieur aan de groep die alleen de chemo kreeg. De cijfers van hartfalen en kansen op leukemie van de groep die ook antracycline chemo plus herceptin kreeg waren significant groter dan van de groep die de niet op antracycline chemo plus herceptin kregen (P<0.001). 7 gevallen van leukemie werden gerapporteerd in de antracycline chemo groep tegenover 1 in de andere chemogroep.

Hier het abstract van de studie waarvan het volledige studierapport te lezen is als u hier klikt.

The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer. The risk–benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia

Adjuvant Trastuzumab in HER2-Positive Breast Cancer

Dennis Slamon, M.D., Ph.D., Wolfgang Eiermann, M.D., Nicholas Robert, M.D., Tadeusz Pienkowski, M.D., Miguel Martin, M.D., Michael Press, M.D., Ph.D., John Mackey, M.D., John Glaspy, M.D., Arlene Chan, M.D., Marek Pawlicki, M.D., Tamas Pinter, M.D., Vicente Valero, M.D., Mei-Ching Liu, M.D., Guido Sauter, M.D., Gunter von Minckwitz, M.D., Frances Visco, J.D., Valerie Bee, M.Sc., Marc Buyse, Sc.D., Belguendouz Bendahmane, M.D., Isabelle Tabah-Fisch, M.D., Mary-Ann Lindsay, Pharm.D., Alessandro Riva, M.D., and John Crown, M.D. for the Breast Cancer International Research Group

N Engl J Med 2011; 365:1273-1283October 6, 2011

Background

Trastuzumab improves survival in the adjuvant treatment of HER-positive breast cancer, although combined therapy with anthracycline-based regimens has been associated with cardiac toxicity. We wanted to evaluate the efficacy and safety of a new nonanthracycline regimen with trastuzumab.

Methods

We randomly assigned 3222 women with HER2-positive early-stage breast cancer to receive doxorubicin and cyclophosphamide followed by docetaxel every 3 weeks (AC-T), the same regimen plus 52 weeks of trastuzumab (AC-T plus trastuzumab), or docetaxel and carboplatin plus 52 weeks of trastuzumab (TCH). The primary study end point was disease-free survival. Secondary end points were overall survival and safety.

Results

At a median follow-up of 65 months, 656 events triggered this protocol-specified analysis. The estimated disease-free survival rates at 5 years were 75% among patients receiving AC-T, 84% among those receiving AC-T plus trastuzumab, and 81% among those receiving TCH. Estimated rates of overall survival were 87%, 92%, and 91%, respectively. No significant differences in efficacy (disease-free or overall survival) were found between the two trastuzumab regimens, whereas both were superior to AC-T. The rates of congestive heart failure and cardiac dysfunction were significantly higher in the group receiving AC-T plus trastuzumab than in the TCH group (P<0.001). Eight cases of acute leukemia were reported: seven in the groups receiving the anthracycline-based regimens and one in the TCH group subsequent to receiving an anthracycline outside the study.

Conclusions

The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2-positive breast cancer. The risk–benefit ratio favored the nonanthracycline TCH regimen over AC-T plus trastuzumab, given its similar efficacy, fewer acute toxic effects, and lower risks of cardiotoxicity and leukemia. (Funded by Sanofi-Aventis and Genentech; BCIRG-006 ClinicalTrials.gov number, NCT00021255.)

Supported by Sanofi-Aventis and Genentech; a Department of Defense Breast Cancer Innovator Award and funding from the Revlon/UCLA Women's Cancer Program and the Peter and Denise Wittich Breast Cancer Program (to Dr. Slamon); and grants (to Dr. Press) from the U.S. Army Medical Research and Development Command (DAMD-03-1-0626), the National Cancer Institute (CA 48780), and the California Breast Cancer Research Program (12IB-0155 and 14NB-0179) for studies of TOP2A.

trastuzumab, herceptin, antracycline, chemo