Common Adverse Effects of Anti-HER2 Therapies and Practical Management Recommendations

Aarti S. Bhardwaj, MD, and Amy D. Tiersten, MD
Published: Wednesday, Mar 12, 2014


There have been remarkable advances in the field of anti-HER2 biologic agents. The benefits of trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1) have all been well studied, but each drug also has its own set of complications and toxicities. Most concerning for trastuzumab is cardiotoxicity; understanding how to monitor for and treat cardiotoxicity is paramount. Diarrhea and rash are potentially troubling side effects seen with lapatinib. Pertuzumab has not been shown to have a high frequency of cardiotoxicity, but cytopenias, diarrhea, and rash can be seen with this medication. With T-DM1, rash and diarrhea are less-common side effects, but thrombocytopenia and transaminitis can be problematic. It is important to know what side effects to monitor for and how to properly manage them in order to best support patients through these biologic treatments. In this review, we discuss the main adverse-event profile of each biologic agent and provide concise management recommendations.
Breast Cancer


Targeted biologic agents may increase efficacy with less toxicity as compared with traditional cytotoxic chemotherapy. Currently there are four targeted agents that are US Food and Drug Administration (FDA)-approved for clinical use for human epidermal growth factor receptor 2 (HER2)-positive breast cancer: trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1). However, these agents have potentially serious toxicities (Table 1). Knowledge of common complications or adverse events (AEs) will enable oncologists to make more informed treatment decisions for each individual patient. The objectives of this review are to provide a current description of the safety profiles of anti- HER2-targeted agents used in breast cancer, and to outline practical recommendations for management of toxicities.

Table 1. Common or Severe Toxicities of Anti-HER2 Biologic Agents

Anti-HER2 Agent Common or Serious Grade 3/4 Adverse Events
Trastuzumab Cardiotoxicity
Infusion reactions
Lapatinib Diarrhea
Pertuzumab Neutropenia
Febrile neutropenia
T-DM1 Thrombocytopenia
Elevated AST
Elevated ALT


The HER2/neu gene is localized to chromosome 17q. It encodes a transmembrane tyrosine kinase receptor protein that belongs to the epidermal growth factor receptor (EGFR) or HER family of four transmembrane receptor tyrosine kinases that mediate cell growth, differentiation, and survival.1,2 Overexpression of the HER2/neu protein, amplification of the HER2/neu gene, or both occur in 20%-25% of breast cancers.3,4 Prior to the development of anti-HER2 agents, HER2- positive breast cancer was known to be aggressive and have high recurrence rates and short disease-free intervals after adjuvant chemotherapy.5


Trastuzumab is a humanized monoclonal antibody and was the first anti-HER2 agent to be approved in 1998, and then in 2006 for HER2-positive breast cancer in the metastatic and adjuvant settings, respectively.6,7 It has been proven to be effective in several neoadjuvant, adjuvant, and metastatic clinical trials. It was first noted in a phase III trial in the metastatic setting that the addition of trastuzumab compared with chemotherapy alone (doxorubicin or epirubicin plus cyclophosphamide or paclitaxel) increased progression-free survival (PFS) by almost 3 months, prolonged overall survival (OS) from 20.3 to 25.1 months, and resulted in a 20% reduction in death.8

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