Neratinib for the treatment of HER2-positive early stage breast cancer

ABSTRACT

Introduction: Despite the advances in the treatment of HER2-positive breast cancer, resistance to actual chemotherapeutic regimens eventually occurs. Neratinib, an orally available pan-inhibitor of the ERBB family, represents an interesting new option for early-stage HER2-positive breast cancer.

Areas covered: In this article, the development of neratinib, with a special focus on its potential value in the treatment of early-stage HER2-positive breast cancer, has been reviewed. For this purpose, a literature search was conducted, including preclinical studies, early-phase trials in advanced cancer with neratinib in monotherapy and in combination, and phase II and large phase III trials in the early setting. Management of neratinib-induced toxicity, future perspectives for the drug, and ongoing trials are also discussed in this review.

Expert commentary: Neratinib is emerging as a promising oral drug for the treatment of HER2-positive breast cancer. Although FDA and EMA approval is derived from the extended adjuvant treatment, this setting may not be the ideal scenario to obtain the beneficial effects of neratinib. Confirmatory data in the neoadjuvant setting and subgroup analysis from the ExTENET trial might bring some light into the best setting for neratinib therapy. Data from confirmatory trials in the metastatic setting are also required.

KEYWORDS:

• Neratinib
• HER2
• early-stage
• adjuvant
• extended therapy

Information resources

• The ExteNET represents the most important trial as pending neratinib approval in the early setting is based on its favorable results [67].

• In addition, the I-SPY 2 and NSABP-FB7 trials provide evidence for potential neratinib value in the neoadjuvant setting [62,63].

• The combination of neratinib and paclitaxel as first-line treatment for HER2+ metastatic breast cancer achieved similar overall efficacy than paclitaxel and trastuzumab, although showed a trends toward delaying CNS relapses [60].

• Management of neratinib-induced diarrhea could be revised in this paper [74].

Ongoing clinical trials with neratinib should be consulted in www.ClinicalTrials.gov.

Declaration of interest

The authors have no 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.

Additional information

Funding

This work has received no funding.