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

Kathy D. Miller, Véronique Diéras, Nadia Harbeck, Fabrice Andre, Reshma L. Mahtani, Luca Gianni, Kathy S. Albain, Diana Crivellari, Liang Fang, Glenn Michelson, Sanne L. De Haas, Howard A. Burris

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58 Scopus citations

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 advancedMBChad 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.

Original languageEnglish (US)
Pages (from-to)1437-1444
Number of pages8
JournalJournal of Clinical Oncology
Volume32
Issue number14
DOIs
StatePublished - May 1 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Miller, K. D., Diéras, 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. (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. Journal of Clinical Oncology, 32(14), 1437-1444. https://doi.org/10.1200/JCO.2013.52.6590