Human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer: how the latest results are improving therapeutic options

Abstract

Human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (MBC) remains an incurable disease, and approximately 25% of patients with HER2+ early breast cancer still relapse after adjuvant trastuzumab-based treatment. HER2 is a validated therapeutic target that remains relevant throughout the disease process. Recently, a number of novel HER2 targeted agents have become available, including lapatinib (a small molecule tyrosine kinase inhibitor of both HER2 and the epidermal growth factor receptor), pertuzumab (a new anti-HER2 monoclonal antibody) and ado-trastuzumab emtansine (T-DM1, a novel antibody-drug conjugate), which provide additional treatment options for patients with HER2+ MBC. The latest clinical trials have demonstrated improved outcome with treatment including pertuzumab or T-DM1 compared with standard HER2 targeted therapy. Here we review the clinical development of approved and investigational targeted agents for the treatment of HER2+ MBC, summarize the latest results of important clinical trials supporting use of these agents in the treatment of HER2+ MBC, and discuss how these results impact therapeutic options in clinical practice.

Whether HER2-positive non-breast cancers are candidates for treatment with Ado-trastuzumab emtansine?

“…Several clinical trials showed the beneficiary effects of T-DM1 in the HER2-positive metastatic setting and in patients with prior exposure to trastuzumab and lapatinib. [40]…”

Precision Oncology Medicine: The Clinical Relevance of Patient‐Specific Biomarkers Used to Optimize Cancer Treatment

“…A comparison of T‐DM1 to lapatinib and capecitabine in the second‐line treatment setting showed that T‐DM1 had less toxicity and a significant OS improvement (30.9 months vs 25.1 months, HR 0.68, 95%CI 0.55 to 0.85, P < .001) . In current practice, T‐DM1 is the preferred second‐line therapy for HER2‐positive metastatic breast cancer …”

“…29 In current practice, T-DM1 is the preferred second-line therapy for HER2-positive metastatic breast cancer. 30 Current clinical practice guidelines recommend HER2 testing on every primary invasive breast cancer and on metastatic sites (if stage IV and specimen becomes available), especially in patients who previously tested HER2 negative and present with disease recurrence. The decision to recommend HER2-targeted treatment should be delayed if HER2 status cannot be determined and additional testing to establish tumor HER2 status is necessary to guide therapeutic decisions.…”

“…Oncotype DX, a 21-gene expression (including HER2 amplification) RT-PCR assay, is used to estimate a woman's risk of recurrence of early-stage, hormone-receptor-positive breast cancer. The assay generates a score ranking a patient's 10-year risk of recurrence in a range from low (<18) through intermediate (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) to high (>30) risk category patients, to also determine whether the addition of chemotherapy is beneficial after breast cancer surgery. 95 Several studies have evaluated the utility of the Oncotype DX test.…”

Late Administration of Trastuzumab Emtansine Might Lead to Loss of Chance for Better Outcome in Patients with HER2-Positive Metastatic Breast Cancer

“…Currently, trastuzumab, pertuzumab, lapatinib, and trastuzumab emtansine (T-DM1) are approved for use in different clinical settings in patients with HER2-positive breast cancer. All of the above inhibit the HER2 pathway, albeit using different strategies [12,13]. Trastuzumab is a recombinant humanized monoclonal antibody that binds the extracellular subdomain IV with internalization and degradation of the HER2 receptor.…”