Universität zu Köln

Miller, Kathy D., Dieras, Veronique, Harbeck, Nadia, Andre, Fabrice, Mahtani, Reshma L., Gianni, Luca, Albain, Kathy S., Crivellari, Diana, Fang, Liang, Michelson, Glenn, de Haas, Sanne L. and Burris, Howard A. (2014). Phase IIa Trial of Trastuzumab Emtansine With Pertuzumab for Patients With Human Epidermal Growth Factor Receptor 2-Positive, Locally Advanced, or Metastatic Breast Cancer. J. Clin. Oncol., 32 (14). S. 1437 - 1446. ALEXANDRIA: AMER SOC CLINICAL ONCOLOGY. ISSN 1527-7755

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Abstract

Purpose Our phase IIa study characterized the safety and efficacy of two human epidermal growth factor receptor 2 (HER2) -targeted agents, trastuzumab emtansine (T-DM1) and pertuzumab, in patients with HER2-positive metastatic breast cancer (MBC). Patients and Methods Patients with HER2-positive locally advanced breast cancer or MBC were treated with 3.6 mg/kg T-DM1 plus pertuzumab (840-mg loading dose, then 420 mg subsequently) once every 3 weeks. The primary efficacy end point was investigator-assessed objective response rate (ORR). Results Sixty-four patients (43 patients in the second-line or greater setting [advanced MBC]; 21 patients in the first-line setting [first-line MBC]) were enrolled. Patients with advanced MBC had received trastuzumab and a median of six prior nonhormonal treatments for MBC; 86% of first-line MBC patients had received trastuzumab in the (neo)adjuvant setting. The ORR was 41% overall, 33% in patients with advanced MBC, and 57% in first-line patients. Median progression-free survival was 6.6, 5.5, and 7.7 months, respectively. The most common adverse events were fatigue (61%), nausea (50%), and diarrhea (39%). The most frequent grade 3 adverse events were thrombocytopenia (13%), fatigue (11%), and liver enzyme elevations (increased ALT: 9%; increased AST: 9%). One patient had left ventricular ejection fraction of less than 40% after study drug discontinuation. Exploratory biomarker analyses demonstrated that patients with above-median tumor HER2 mRNA levels had a numerically higher ORR than patients with below-median levels (44% v 33%, respectively). Conclusion T-DM1 and pertuzumab can be combined at full doses with no unexpected toxicities. The preliminary efficacy in patients in the first-line and advanced MBC settings warrants further investigation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Miller, Kathy D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Dieras, Veronique UNSPECIFIED UNSPECIFIED UNSPECIFIED Harbeck, Nadia UNSPECIFIED UNSPECIFIED UNSPECIFIED Andre, Fabrice UNSPECIFIED UNSPECIFIED UNSPECIFIED Mahtani, Reshma L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gianni, Luca UNSPECIFIED UNSPECIFIED UNSPECIFIED Albain, Kathy S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Crivellari, Diana UNSPECIFIED UNSPECIFIED UNSPECIFIED Fang, Liang UNSPECIFIED UNSPECIFIED UNSPECIFIED Michelson, Glenn UNSPECIFIED UNSPECIFIED UNSPECIFIED de Haas, Sanne L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Burris, Howard A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-438399
DOI:	10.1200/JCO.2013.52.6590
Journal or Publication Title:	J. Clin. Oncol.
Volume:	32
Number:	14
Page Range:	S. 1437 - 1446
Date:	2014
Publisher:	AMER SOC CLINICAL ONCOLOGY
Place of Publication:	ALEXANDRIA
ISSN:	1527-7755
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SINGLE-AGENT PERTUZUMAB; DIMERIZATION INHIBITOR; PLUS DOCETAXEL; DOUBLE-BLIND; RHUMAB 2C4; OPEN-LABEL; LAPATINIB; EFFICACY; SAFETY; COMBINATION Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43839