Combination therapies for the treatment of HER2-positive breast cancer: current and future prospects. Issue 7 (3rd July 2018)

• Record Type: Journal Article
• Authors: Brandão, Mariana; Pondé, Noam F.; Poggio, Francesca; Kotecki, Nuria; Salis, Mauren; Lambertini, Matteo; de Azambuja, Evandro
• Is Part Of: Expert review of anticancer therapy. Volume 18:Issue 7(2018)
• Page Start: 629
• Page End: 649
• Publication Date: 2018-07-03
• Subjects: Breast neoplasms -- HER2-positive -- trastuzumab -- cost-benefit analysis -- quality of life; Cancer -- Treatment -- Periodicals; 616.99406
• DOI: 10.1080/14737140.2018.1477596
• Languages: English
• ISSNs: 1473-7140

Abstract

ABSTRACT: Introduction : HER2-positive disease is an aggressive subtype of breast cancer that has been revolutionized by anti-HER2 directed therapies. Multiple drugs have been developed and are currently in clinical use, including trastuzumab, lapatinib, pertuzumab, T-DM1, and neratinib, alone or combined in 'dual HER2-blockade' regimens. Areas covered : A comprehensive literature review was performed regarding the current state and the future of combination regimens containing anti-HER2 agents, focusing on their efficacy, toxicity, and cost-effectiveness. Expert commentary : The combination of trastuzumab/pertuzumab is approved in all disease settings, while trastuzumab/neratinib is approved in the adjuvant setting and trastuzumab/lapatinib in metastatic disease. Meanwhile, as breast cancer biology and resistance mechanisms become clearer, combinations with drugs like PI3K/Akt/mTOR inhibitors, CDK4/6 inhibitors, anti-PD(L)1 antibodies, endocrine therapy, and new anti-HER2 agents (panHER and HER2 tyrosine kinase inhibitors, bispecific antibodies, anti-HER3 antibodies, and antibody-drug conjugates) are being extensively tested in clinical trials. More specific strategies for the 'triple-positive' (estrogen receptor-positive/HER2-positive) disease are also being explored. However, there is an urgent need for the development of predictive biomarkers for a better tailoring of anti-HER2 directed therapy. This is the only way to further improve clinical outcomes and quality of life and to decrease costs and toxicities of unnecessary treatments.