Investigational drugs in early stage clinical trials for the treatment of HER2+ breast cancer

ABSTRACT

Introduction: Despite improvements in the management of HER2+ breast cancer, metastatic disease is still fatal. Usually, these patients receive several lines of chemotherapy associated with HER2 targeted treatments. Most of the trials using innovative approaches are positioning themselves in disease that is resistant to pertuzumab and trastuzumab emtansine (TDM1).

Areas covered: We describe the recent advances in clinical development of anti-HER2 treatments. To this aim, we used literature search via Pubmed and made an inventory of abstracts published during the last two years in major oncology conferences.

Expert opinion: Further changes will probably occur during the next decade in the management of metastatic HER2-positive breast cancer. This is mainly driven by the fact that the two mainstay drugs (pertuzumab and TDM-1) that confer prolonged survival (56 months) to these patients are currently being used in the treatment of early-stage disease in a subset of patients. Thus, there is an urgent need to develop new, innovative approaches in those patients whose disease has become resistant to these highly potent drugs. Several new antibody-drug conjugates, bispecific antibodies or new generation tyrosine kinase inhibitor (TKIs) hold promise and should be assessed and compared with drugs currently used.

KEYWORDS:

• HER2+ breast cancer
• ADCs
• bispecific antibodies
• TKIs

Article Highlights

• Despite the improvement in the outcomes of patients with HER2-positive metastatic breast cancer with the available anti-HER2 targeted agents, metastatic disease is still occurring and has a fatal outcome.

• Newly developed innovative antibody-drug conjugates, bispecific antibodies and TKIs with potential penetration of the central nervous system (CNS) show interesting results in heavily pre-treated patients and will probably change the management of metastatic HER2-positive breast cancer.

• Tumors with HER2 low expression can also respond to some of these new agents because of their higher affinity, specificity and bystander effect.

• Combinations of anti-HER2 therapies with other agents (immunotherapy, CDK4/6 inhibitors, selective PI3K inhibitors) needs further evaluation.

• Better understanding of tumor biology can lead to further segmentations of HER2-positive breast cancer and further personalize treatment.

This box summarizes key points contained in the article.

Declaration of interest

A Awada has served on Advisory boards for and has received travel grants and speaker fees from Novartis, Roche, Lilly, Amgen, EISAI, BMS, Pfizer, MSD, Leopharma and Genomic Health. 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

One peer reviewer receives institutional research funding from Novartis, Genentech, Eli Lilly, Pfizer, Merck, Exelixis, Eisai, Bristol Meyers Squibb, AstraZeneca, Cyclacel, Immunomedics, Odenate, and Nektar and has served as an advisor/consultant to Novartis, Eli Lilly, Pfizer, Merck, AstraZeneca, Eisai, Puma, Genentech, Immunomedics, Nektar, Tesaro, and Nanostring. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.