New agents for the management of resistant metastatic breast cancer

ABSTRACT

Introduction: Metastatic breast cancer (MBC) is an incurable disease and treatment is directed towards symptom palliation and survival prolongation. Treatment selection in patients is based on tumor biology, age, comorbidities, performance status, tumor burden, and prior treatment history.

Areas covered: This present review summarizes the recent treatment strategies in the management of MBC, highlighting regimens after first-line therapy. Topics discussed include new strategies for endocrine therapy, anti-HER2 therapy, and promising strategies for the management of triple negative breast cancer.

Expert opinion: MBC is a heterogeneous entity and despite recent advances, there is significant room for improvement of treatment beyond first-line therapies. Combination regimens that can maximize clinical efficacy while minimizing toxicities are required. Current investigation approaches in advanced stages of clinical development include immunoconjugates, immune checkpoint blockade, novel cyclin-dependent-kinase inhibitors, and PARP inhibitors for MBC associated with germline BRCA mutations. We recommend that every patient with MBC should be evaluated for clinical trial options.

KEYWORDS:

• Breast cancer
• metastatic
• endocrine therapy
• chemotherapy
• anti-HER2 therapy
• advanced

Article highlights

• MBC is an incurable disease, although systemic therapies improve survival and may palliate or delay the onset of tumor-associated symptoms. Factors that might be considered in selecting therapy include tumor biology, age, comorbidities, performance status, tumor burden, and prior treatment history.

• In ER+, the recommended regimens for second-line are everolimus plus exemestane or fulvestrant, or fulvestrant plus palbociclib, depending on the regimen received in first-line.

• In HER2+, T-DM1 is the preferred second-line regimen after progression on standard first-line pertuzumab, trastuzumab and a taxane. Lapatinib, trastuzumab, or capecitabine combinations with or without chemotherapy could be used after T-DM1 resistance.

• In TNBC, cytotoxic therapy remains the only therapeutic options. Some evidence indicates that eribulin improves OS compared with other options, and should be considered after first-line therapy.

• Every patient with MBC should be evaluated for clinical trial options. Current investigation approaches in advanced stages of clinical development include immunoconjugates, immune checkpoint blockade, novel CDK inhibitors, and PARP inhibitors for MBC associated with germline BRCA mutations.

This box summarizes key points contained in the article.

Acknowledgments

The manuscript development is supported by The Einstein Paul Calabresi Career Development Program (NIH 5K12CA132783-08) and NIH/National Center for Advancing Translational Science (NCATS) Einstein-Montefiore CTSA (Grant Number UL1TR001073).

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.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not received any funding.