Adjuvant therapeutic approaches of HER2-positive breast cancer with a focus on neratinib maleate

ABSTRACT

Introduction: Breast cancer (BC) is the most common cancer in women. Human epidermal growth factor receptor 2-positive (HER2-positive) BC represents up to 15% of all BC cases and is associated with a poor prognosis. Despite the substantial improvement obtained with the addition to the treatment of trastuzumab in this subtype of BC, disease recurrence can still occur.

Areas covered: Anti-HER2 targeting drugs such as trastuzumab, pertuzumab, and T-DM1 have shown significant results in (neo)adjuvant setting. In this article, we will focus on available data for neratinib to reduce BC recurrence based mainly on the results of the ExteNET trial. This trial aimed to investigate whether neratinib can further reduce the risk of recurrence of patients diagnosed with HER2-positive BC. This trial demonstrated a significant reduction in the risk of invasive disease-free survival, particularly in hormone receptor-positive population. In addition, this review provides an expert opinion and analysis of the current situation in the adjuvant HER2-positive BC setting and in particular the escalation strategy of HER2 targeting.

Expert opinion: The treatment landscape of HER2 positive BC in this setting will evolve in the coming years with a need for clinical and molecular perspective tools to guide therapy.

KEYWORDS:

• Her2 positive breast cancer
• escalation strategies
• adjuvant
• neratinib

Acknowledgments

The authors acknowledge the contribution of Ornella Martini for English language editing of this article and Puma Biotechnology for providing some of the references.

Article highlights

• Neratinib is an irreversible multi-tyrosine kinase inhibitor of HER1, HER2, and HER4.

• Neratinib showed substantial clinical activity in metastatic HER2-positive BC as monotherapy and in combination with chemotherapy compounds.

• Neratinib, TDM1, and pertuzumab showed an improvement in outcome when added to traditional HER2-targeted adjuvant therapy.

• Neratinib was shown to improve invasive DFS in HER2-positive early BC patients at the expense of considerable diarrhea necessitating primary prophylactic loperamide.

• The benefit of extended neratinib after one year of trastuzumab and pertuzumab or TDM-1 still has to be determined taking into consideration the implication costs and financial toxicity.

• The landscape of adjuvant HER2-positive BC might further evolve in the coming years and it will be of utmost importance to develop clinical and molecular predictive tools to guide adjuvant treatment in this field.

Declaration of interest

A Awada has received honoraria and is an Advisory Board member for Puma Biotechnology and Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript declares participating in a clinical study using neratinib. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded