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Pertuzumab in the treatment of HER2-positive breast cancer: an evidence-based review of its safety, efficacy, and place in therapy

Authors Ishii K, Morii N, Yamashiro H

Received 31 May 2019

Accepted for publication 1 August 2019

Published 31 October 2019 Volume 2019:14 Pages 51—70


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Professor Garry Walsh

Kei Ishii, Nao Morii, Hiroyasu Yamashiro

Department of Breast Surgery, Tenri Hospital, Tenri, Japan

Correspondence: Kei Ishii
Breast Surgery, Tenri Hospital, 200, Mishima town, Tenri City, Nara Prefecture 632-0015, Japan
Tel +81 74 363 5611

Abstract: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a distinct subset of breast cancer that results from overexpression of HER2 protein. Pertuzumab—a recombinant humanized monoclonal antibody that binds to the extracellular dimerization domain II of HER2—was recently approved for adjuvant therapy and neoadjuvant therapy of HER2-positive early breast cancer. As pertuzumab and trastuzumab bind to different domains of the extracellular dimerization domain of HER2, a combination therapy of pertuzumab and trastuzumab is beneficial for the treatment of metastatic cancer, advanced local cancer, or early cancer by dual HER2 blockage. Many clinical trials have been performed using pertuzumab for breast cancer patients; these include the CLEOPATRA trial for palliative therapy, the APHINITY trial for adjuvant therapy, and the NeoSphere and the TRYPHAENA trials for neoadjuvant therapy. These trials revealed pertuzumab to be a safe and effective drug regardless of the patient age and hormone receptor status. Notably, pertuzumab use was associated with severe cardiac toxicity in some cases; however, the risk of pertuzumab-induced cardiac dysfunction was low. The most common adverse effect associated with pertuzumab-use was diarrhea, but most cases were not severe. Several different chemotherapeutic agents have been investigated to determine optimal chemotherapeutic combinations for dual HER2 blockage. Some exploratory analyses indicate that pertuzumab treatment offered little benefit to patients with node-negative and small primary tumors; pertuzumab treatment was also found not be cost-effective. Further research will reveal the appropriate usage of pertuzumab for treating a subset of eligible patients.

Keywords: pertuzumab, HER2, breast cancer, trastuzumab

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