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J Clin Oncol. 2015 Apr 1;33(10):1136-42. doi: 10.1200/JCO.2014.58.7782. Epub 2015 Feb 23.

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.

Author information

1
Ian E. Krop, Dana-Farber Cancer Institute, Boston, MA; Thomas M. Suter, Bern University Hospital, Bern, Switzerland; Chau T. Dang, Memorial Sloan Kettering Cancer Center, New York; Marc L. Citron, Hofstra North Shore-Long Island Jewish School of Medicine, New Hyde Park, NY; Luc Dirix, Sint-Augustinus Hospital, Antwerp, Belgium; Gilles Romieu, Institut du Cancer de Montpellier Val d'Aurelle, Montpellier; Mario Campone, Institut de Cancérologie de l'Ouest/René Gauducheau, Nantes Saint-Herblain, France; Claudio Zamagni, Policlinico Sant'Orsola-Malpighi Hospital, Bologna; Luca Gianni, San Raffaele Hospital, Milan, Italy; and Na Xu and Melanie Smitt, Genentech, South San Francisco, CA. ian_krop@dfci.harvard.edu.
2
Ian E. Krop, Dana-Farber Cancer Institute, Boston, MA; Thomas M. Suter, Bern University Hospital, Bern, Switzerland; Chau T. Dang, Memorial Sloan Kettering Cancer Center, New York; Marc L. Citron, Hofstra North Shore-Long Island Jewish School of Medicine, New Hyde Park, NY; Luc Dirix, Sint-Augustinus Hospital, Antwerp, Belgium; Gilles Romieu, Institut du Cancer de Montpellier Val d'Aurelle, Montpellier; Mario Campone, Institut de Cancérologie de l'Ouest/René Gauducheau, Nantes Saint-Herblain, France; Claudio Zamagni, Policlinico Sant'Orsola-Malpighi Hospital, Bologna; Luca Gianni, San Raffaele Hospital, Milan, Italy; and Na Xu and Melanie Smitt, Genentech, South San Francisco, CA.

Abstract

PURPOSE:

Trastuzumab emtansine (T-DM1), an antibody-drug conjugate comprising the cytotoxic agent DM1, a stable linker, and trastuzumab, has demonstrated substantial activity in human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer, raising interest in evaluating the feasibility and cardiac safety of T-DM1 in early-stage breast cancer (EBC).

PATIENTS AND METHODS:

Patients (N = 153) with HER2-positive EBC and prechemotherapy left ventricular ejection fraction (LVEF) ≥ 55% received (neo)adjuvant doxorubicin plus cyclophosphamide or fluorouracil plus epirubicin plus cyclophosphamide followed by T-DM1 for four cycles. Patients could then receive three to four cycles of optional docetaxel with or without trastuzumab. T-DM1 was then resumed with optional radiotherapy (sequential or concurrent) for 1 year (planned) of HER2-directed therapy. The coprimary end points were rate of prespecified cardiac events and safety.

RESULTS:

Median follow-up was 24.6 months. No prespecified cardiac events or symptomatic congestive heart failures were reported. Four patients (2.7%) had asymptomatic LVEF declines (≥ 10 percentage points from baseline to LVEF < 50%), leading to T-DM1 discontinuation in one patient. Of 148 patients who received ≥ one cycle of T-DM1, 82.4% completed the planned 1-year duration of HER2-directed therapy. During T-DM1 treatment, 38.5% and 2.7% of patients experienced grade 3 and 4 adverse events, respectively. Approximately 95% of patients receiving T-DM1 plus radiotherapy completed ≥ 95% of the planned radiation dose with delay ≤ 5 days.

CONCLUSION:

Use of T-DM1 for approximately 1 year after anthracycline-based chemotherapy was feasible and generally well tolerated by patients with HER2-positive EBC, providing support for phase III trials of T-DM1 in this setting.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01196052.

PMID:
25713436
PMCID:
PMC5657012
DOI:
10.1200/JCO.2014.58.7782
[Indexed for MEDLINE]
Free PMC Article

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