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HER2 Biological Pathways Reviews
HER2
ERBB2; CD340; HER-2; HER-2/neu; HER2; MLN 19; NEU; NGL; TKR1; erb-b2 receptor tyrosine kinase 2
Human epidermal growth factor receptor 2 (HER2) is 1 of 4 transmembrane tyrosine kinase receptor proteins in the epidermal growth factor receptor family.1,2 Normally expressed on epithelial cellular membranes of organs such as breast and skin, HER2 exists in other tissues, including gastrointestinal, respiratory, reproductive, urinary tract tissues, and more.2,3
HER2-positive status is both a prognostic indicator of poor outcomes and predictive biomarker of treatment response to HER2-targeted therapies.2,4 The effectiveness of emerging therapies, such as HER2-specific antibodies and antibody-drug conjugates, somewhat depends on the ability of agents to bind to cell surface targets then efficiently internalize and accumulate the cytotoxic agent while preserving host tissues.4
Understanding the Role of HER2
This animation explains the role of HER2 in the regulation of cell growth and the negative effects of HER2 overexpression.
Expression in Cancer
HER2-positivity is found in a variety of cancer types. The graphic below displays the expression of HER2-positivity in up to a certain percentage of cases in each cancer type.
HER2 Targeting Anticancer Drugs
Anti-HER2 therapies block HER2 receptors from receiving growth signals, thus slowing or stopping the growth of cancer cells. This table outlines therapies targeting HER2 both approved by the FDA and in the pipeline.
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HER2 Targeting Anticancer Drugs Approved by the FDAa |
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Brand Name (Generic Drug Name) |
Indications |
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Enhertu (fam-trastuzumab deruxtecan-nxki)1 |
Treatment of adults with HER2-positive, unresectable or metastatic breast cancer who received a prior anti-HER2-based regimen in the metastatic setting or in the neoadjuvant or adjuvant setting and had disease recurrence during or within 6 months of completing therapy |
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Treatment of adults with HER2-low, unresectable or metastatic breast cancer who received a prior chemotherapy in the metastatic setting or had disease recurrence during or within 6 months of completing adjuvant chemotherapy |
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Treatment of adults with HER2-positive, unresectable or metastatic NSCLC who have received prior systemic therapy |
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Treatment of adults with HER2-positive, locally advanced or metastatic gastric or GEJ adenocarcinoma who received a prior trastuzumab-based regimen |
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Herceptin (trastuzumab)2 |
Adjuvant treatment of adults with HER2-overexpressing, node-positive or node-negative breast cancer as part of a regimen consisting of doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; as part of a treatment regimen with docetaxel and carboplatin; or as a single agent following multi-modality anthracycline-based therapy, based on an FDA-approved companion diagnostic for trastuzumab |
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In combination with paclitaxel for the treatment of adults with HER2-overexpressing metastatic breast cancer in the first-line or as a single agent for HER2-overexpressing breast cancer in patients who received ≥1 chemotherapy regimens for metastatic disease |
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Herceptin Hylecta (trastuzumab + hyaluronidase-oysk)3 |
Adjuvant treatment of adults with HER2 overexpressing, node-positive or node-negative breast cancer as part of a regimen comprising doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; as part of a regimen with docetaxel and carboplatin; or as a single agent following multi-modality anthracycline-based therapy |
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In combination with paclitaxel for the first-line treatment of adults with HER2-overexpressing, metastatic breast cancer, or as a single agent for the treatment of adults with HER2-overexpressing breast cancer who received ≥1 chemotherapy regimens for metastatic disease |
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Herzuma (trastuzumab-pkrb)4 |
Adjuvant treatment of HER2-overexpressing, node-positive or node-negative breast cancer as part of a regimen comprising doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel; as part of a regimen with docetaxel and carboplatin; or as a single agent following multi-modality anthracycline-based therapy, based on an FDA-approved companion diagnostic for trastuzumab |
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In combination with paclitaxel for the first-line treatment of HER2-overexpressing, metastatic breast cancer or as a single-agent for the treatment of HER2-overexpressing breast cancer in patients who received ≥1 chemotherapy regimens for metastatic disease, based on an FDA-approved companion diagnostic trastuzumab |
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In combination with cisplatin and capecitabine or 5-fluorouracil for the treatment of patients with HER2 overexpressing, metastatic gastric, or GEJ adenocarcinoma who have not previously received treatment for metastatic disease, based on an FDA-approved companion diagnostic for trastuzumab |
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Kadcyla (ado-trastuzumab emtansine)5 |
Treatment of patients with HER2-positive, metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination |
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Adjuvant treatment of patients with HER2-positive, early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based therapy |
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Margenza (margetuximab-cmkb)6 |
In combination with chemotherapy for the treatment of adult patients with metastatic HER2-positive breast cancer who have received ≥2 prior anti-HER2 regimens, at least 1 of which was for metastatic disease |
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Nerlynx (neratinib)7 |
Extended adjuvant treatment of adults with early-stage, HER2-positive breast cancer, after adjuvant trastuzumab-based therapy |
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In combination with capecitabine for the treatment of adults with HER2-positive, advanced or metastatic breast cancer who received ≥2 prior anti-HER2 based regimens in the metastatic setting |
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Ogivri (trastuzumab-dkst)8 |
Treatment of HER2-overexpressing breast cancer |
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Treatment of HER2-overexpressing, metastatic gastric or gastroesophageal junction adenocarcinoma |
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Ontruzant (trastuzumab-dttb)9 |
Treatment of HER2-overexpressing breast cancer, based on an FDA-approved companion diagnostic for trastuzumab |
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Treatment of HER2-overexpressing, metastatic gastric or gastroesophageal junction adenocarcinoma, based on an FDA-approved companion diagnostic for trastuzumab |
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Perjeta (pertuzumab)10 |
In combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive, metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease |
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In combination with trastuzumab and chemotherapy as neoadjuvant treatment for patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer as part of a complete regimen for early breast cancer or as adjuvant treatment for patients with HER2-positive, early breast cancer at high risk for recurrence |
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Phesgo (pertuzumab, trastuzumab, + hyaluronidase-zzxf)11 |
In combination with chemotherapy as neoadjuvant treatment for patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer as part of a complete regimen for early breast cancer or as adjuvant treatment for patients with HER2-positive, early breast cancer at high risk for recurrence |
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In combination with docetaxel for the treatment of patients with HER2-positive, metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease |
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Trazimera (trastuzumab-qyyp)12 |
Treatment of HER2-overexpressing breast cancer, based on an FDA-approved companion diagnostic for trastuzumab |
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Treatment of HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, based on an FDA-approved companion diagnostic for trastuzumab |
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Tukysa (tucatinib)13 |
In combination with trastuzumab and capecitabine for the treatment of adults with advanced, unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who received ≥1 HER2-targeted regimens in the metastatic setting |
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Tykerb (lapatinib)14 |
In combination with capecitabine for the treatment of patients with advanced or metastatic breast cancer that overexpresses HER2 who received prior therapy, including an anthracycline, a taxane, and trastuzumab |
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In combination with letrozole for the treatment of postmenopausal women with HR-positive, metastatic breast cancer that overexpresses HER2 for whom hormonal therapy is indicated |
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Vizimpro (dacomitinib)15 |
First-line treatment of patients with metastatic NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA-approved test |
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HER2 Targeting Anticancer Drugs in the Pipelineb |
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Brand Name (Generic Drug Name) |
Potential Indications |
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Enhertu (fam-trastuzumab deruxtecan-nxki)16 |
Being evaluated for the treatment of patients with HER2-positive breast cancer; HER2-low breast cancer; HER2-positive, unresectable and/or metastatic breast cancer previously treated with standard of care HER2 therapies, including ado-trastuzumab emtansine; HER2-positive, unresectable and/or metastatic breast cancer previously treated with trastuzumab and taxane; HER2-low, unresectable and/or metastatic breast cancer; HER2-positive, high-risk breast cancer; HER2-low, HR-positive breast cancer; HER2-overexpressing, advanced gastric or gastroesophageal junction adenocarcinoma that progressed with 2 prior treatment regimens; HER2-positive gastric cancer; HER2-positive or HER2-over-expressing, unresectable and/or metastatic NSCLC; HER2-positive NSCLC; HER2-positive solid tumors |
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Faslodex (fulvestrant) |
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GDC-0077 (inavolisib)17 |
Being evaluated for the neoadjuvant endocrine treatment of patients with early-stage, HER2-positive, HR-positive, PIK3CA mutant breast cancer |
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OP-125018 |
Being evaluated for the treatment of patients with ER-positive/HER2-positive, metastatic breast cancer with CNS metastases |
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Perjeta (pertuzumab)19 |
Being evaluated in combination with trastuzumab emtansine for the treatment of patients with early, HER2-positive breast cancer; in combination with atezolizumab for the treatment of patients with early, metastatic, HER2-positive breast cancer |
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RG6171 (giredestrant)20 |
Being evaluated in combination with Phesgo (pertuzumab, trastuzumab, + hyaluronidase-zzxf) for the first-line treatment of patients with ER-positive, HER2-positive breast cancer |
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RG6194 (runimotamab)17 |
Being evaluated for the treatment of patients with metastatic, HER2-expressing cancers |
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SAR446309 (formerly known as AMX-818)21 |
Being evaluated for the treatment of patients with solid tumors |
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SHR6390 (dalpiciclib)22 |
Being evaluated for the treatment of patients with HER2-positive gastric cancer |
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Kadcyla (ado-trastuzumab emtansine)17 |
Being evaluated for the first-line treatment of patients with HER2-positive, metastatic breast cancer; in combination with pertuzumab for the treatment of patients with early, HER2-positive breast cancer; in combination with atezolizumab for the treatment of patients with early, HER2-positive breast cancer; in combination with atezolizumab or placebo for the treatment of patients with HER2- and PD-L1–positive locally advanced or metastatic breast cancer previously treated with trastuzumab- (± pertuzumab) and taxane-based therapy; for the treatment of high-risk patients with HER2-positive early breast cancer; for the third-line treatment of patients with HER2-positive, metastatic breast cancer |
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CNS, central nervous system; EGFR, epidermal growth factor receptor; ER, estrogen receptor; ET, endocrine therapy; GEJ, gastroesophageal junction; HR, hormone receptor; NSCLC, non-small-cell lung cancer.
aAdapted from prescribing information.1-15 bAdapted from manufacturer websites.16-22 |
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