Dang, Chau T.
Gianni, Luca
Romieu, Gilles
Dirix, Luc
Campone, Mario
Citron, Marc L.
Zamagni, Claudio
Krop, Ian E.
Xu, Na
Smitt, Melanie
Suter, Thomas
<jats:p> 532 </jats:p><jats:p> Background: T-DM1 has demonstrated clinical activity as a single agent in patients (pts) with previously untreated MBC. In a previous phase II randomized trial of T-DM1 vs trastuzumab + docetaxel, T-DM1 had no clinically significant cardiac events, no cases of post-baseline left ventricular ejection fraction (LVEF) ≤40%, and fewer grade ≥3 adverse events (AEs; Hurvitz, ESMO 2011). This phase II study assessed the clinical safety and feasibility of T-DM1 following anthracycline-based chemotherapy in the adjuvant or neoadjuvant setting for early-stage HER2-positive breast cancer. Methods: TDM4874g (NCT01196052) is a phase II single-arm, open-label study of T-DM1 (3.6 mg/kg q3w IV; up to 17 cycles) following completion of doxorubicin/cyclophosphamide (AC; q2w or q3w for 4 cycles), or 5-fluorouracil/epirubicin (100 mg/m<jats:sup>2</jats:sup>)/cyclophosphamide (FEC; q3w for 3-4 cycles) chemotherapy in pts with early-stage HER2-positive breast cancer. Pre-chemotherapy LVEF by MUGA/ECHO ≥55% was required for enrollment. Co-primary endpoints are safety and rate of pre-specified cardiac events following initiation of T-DM1 treatment. An interim analysis was planned for the first 60 pts evaluable for cardiac safety (received ≥1 T-DM1 dose). Results: For pts in the interim analysis (20 received AC, 40 FEC), the most common all-grade T-DM1-related AEs were nausea (n=20), asthenia (n=17), and headache (n=17); 8 pts had grade 3/4 T-DM1-related AEs (including 3 with grade 3 increased aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]). No deaths occurred. Two pts had AEs leading to T-DM1 discontinuation (grade 3 AST and grade 2 ALT increase; grade 3 thrombocytopenia). No pre-specified cardiac events occurred; no pts delayed or discontinued T-DM1 due to cardiac AEs; there were no reports of grade ≥2 left ventricular systolic dysfunction, heart failure, or LVEF <50%. Results will be updated with data from all 153 enrolled pts. Conclusions: T-DM1 following anthracycline-based chemotherapy was not associated with cardiac toxicity in pts with early-stage HER2-positive breast cancer; this study continues without modification. </jats:p>
https://sonar.ch/global/documents/391
eng
info:eu-repo/semantics/altIdentifier/doi/10.1200/jco.2012.30.15_suppl.532
info:eu-repo/semantics/altIdentifier/issn/0732-183X
Journal of Clinical Oncology. - American Society of Clinical Oncology (ASCO). - 2012, vol. 30, no. 15_suppl, p. 532-532
Cancer Research
Oncology
Cardiac safety in a phase II study of trastuzumab emtansine (T-DM1) following anthracycline-based chemotherapy as adjuvant or neoadjuvant therapy for early-stage HER2-positive breast cancer.
http://purl.org/coar/resource_type/c_6501