Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human epidermal growth factor receptor 2-positive, locally advanced, or metastatic breast cancer Journal Article

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Authors: Miller, K. D.; Dieras, V.; Harbeck, N.; Andre, F.; Mahtani, R. L.; Gianni, L.; Albain, K. S.; Crivellari, D.; Fang, L.; Michelson, G.; de Haas, S. L.; Burris, H. A.
Article Title: Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human epidermal growth factor receptor 2-positive, locally advanced, or metastatic breast cancer
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.
Journal Title: Journal of Clinical Oncology
Volume: 32
Issue: 14
ISSN: 0732-183X
Publisher: Unknown  
Journal Place: United States
Date Published: 2014
Start Page: 1437
End Page: 1444
Language: eng
DOI/URL:

10.1200/JCO.2013.52.6590
Notes: ClinicalTrials.gov/NCT00875979; JID: 8309333; 0 (Antibodies, Monoclonal, Humanized); 14083FR882 (Maytansine); 380610-27-5 (pertuzumab); SE2KH7T06F (ado-trastuzumab emtansine); 2014/04/14 [aheadofprint]; ppublish