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| Gene | ERBB2 |
| Variant | over exp |
| Impact List | none |
| Protein Effect | no effect |
| Gene Variant Descriptions | ERBB2 (HER2) over exp indicates an over expression of the Erbb2 (Her2) protein and/or mRNA. However, the mechanism causing the over expression is unknown. |
| Associated Drug Resistance |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| ERBB2 over exp | stomach cancer | sensitive | BMS-690514 | Preclinical | Actionable | In a preclinical study, BMS-690514 inhibited tumor growth in a gastric cancer xenograft model with ERBB2 (HER2) amplification and overexpression (PMID: 21531814). | 21531814 |
| ERBB2 over exp | colorectal cancer | decreased response | Panitumumab | Clinical Study - Cohort | Actionable | In a retrospective analysis, patients with metastatic KRAS exon 2 wild-type colorectal cancer harboring ERBB2 (HER2) amplification or overexpression (n=79) demonstrated poorer objective response rate (31.2 vs 46.9, p=0.031) and progression-free survival (5.7 vs 7 months, p=0.087) to anti-EGFR treatment (Vectibix (panitumumab) or Erbitux (cetuximab), as monotherapy or combined with chemotherapy) when compared to ERBB2 (HER2)-negative patients (n=113) (PMID: 30952821). | 30952821 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Lapatinib + Trastuzumab | Guideline | Actionable | The combination of Herceptin (trastuzumab) and Tykerb (lapatinib) is included in guidelines for patients with ERBB2 (HER2)-positive advanced breast cancer who progressed on Herceptin (trastuzumab)-based therapy, however, the combination therapy is not recommended as neoadjuvant therapy for ERBB2 (HER2)-positive patients with early breast cancer (PMID: 31236598, PMID: 30032243; ESMO.org). | detail... 30032243 31236598 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Lapatinib + Trastuzumab | Guideline | Actionable | Herceptin (trastuzumab) combined with Tykerb (lapatinib) is included in guidelines as systemic therapy for patients with recurrent or metastatic hormone receptor-positive (ER and/or PR) or negative, ERBB2 (HER2)-positive breast cancer (NCCN.org). | detail... |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Docetaxel + Trastuzumab | Guideline | Actionable | Herceptin (trastuzumab) combined with Taxotere (docetaxel) is included in guidelines as systemic therapy for patients with recurrent or metastatic hormone receptor-positive (ER and/or PR) or negative, ERBB2 (HER2)-positive breast cancer (NCCN.org). | detail... |
| ERBB2 over exp | pancreatic carcinoma | sensitive | ADC ST8176AA1 | Preclinical - Pdx | Actionable | In a preclinical study, ADC ST8176AA1 treatment inhibited tumor growth in patient-derived xenograft (PDX) models of pancreatic carcinoma overexpressing ERBB2 (HER2) (PMID: 32039017). | 32039017 |
| ERBB2 over exp | colorectal cancer | resistant | Cetuximab | Clinical Study - Cohort | Actionable | In a retrospective analysis, patients with metastatic KRAS exon 2 wild-type colorectal cancer harboring ERBB2 (HER2) amplification or overexpression (n=79) demonstrated poorer objective response rate (31.2 vs 46.9, p=0.031) and progression-free survival (5.7 vs 7 months, p=0.087) to anti-EGFR treatment (Vectibix (panitumumab) or Erbitux (cetuximab), as monotherapy or combined with chemotherapy) when compared to ERBB2 (HER2)-negative patients (n=113) (PMID: 30952821). | 30952821 |
| ERBB2 over exp | colorectal cancer | resistant | Cetuximab | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ERBB2 (HER2) over expression was associated with resistance to Erbitux (cetuximab) treatment in a human cell line xenograft model of colorectal cancer (PMID: 26296355). | 26296355 |
| ERBB2 over exp | stomach cancer | sensitive | Dacomitinib | Phase II | Actionable | In a Phase II trial, Vizimpro (dacomitinib) resulted in a 7.4% (2/27) response rate and 40.7% (11/27) disease control rate when treating advanced gastric cancer patients with ERBB2 (HER2) over expression (J Clin Oncol 30, 2012 (suppl 4; abstr 54)). | detail... |
| ERBB2 over exp | stomach cancer | sensitive | Dacomitinib | Preclinical | Actionable | In a preclinical study, ERBB2 (HER2) over expressing gastric cancer cells were sensitive to Vizimpro (dacomitinib), resulting in inhibition of ERBB2 (HER2)/ERBB3 (HER3) heterodimers (PMID: 22135232). | 22135232 |
| ERBB2 over exp | stomach cancer | sensitive | S-222611 | Phase I | Actionable | In a Phase I trial, S-222611 resulted in a complete response in a gastric-esophageal junction cancer patient overexpressing ERBB2 (HER2) and a partial response in a gastric cancer patient also overexpressing ERBB2 (HER2) (J Clin Oncol 33, 2015 (suppl; abstr 2511)). | detail... |
| ERBB2 over exp | carcinoma | predicted - sensitive | Margetuximab | Phase I | Actionable | In a Phase I trial, Margetuximab (MGAH22) treatment resulted in partial responses in 12% (7/60) and stable disease in 50% (30/60) of patients with ERBB2 (HER2)-positive breast or gastric cancer, or other carcinomas that overexpress Erbb2 (Her2) (PMID: 28119295). | 28119295 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Capecitabine + Neratinib | FDA approved | Actionable | In a Phase III (NALA) trial that supported FDA approval, combination of Nerlynx (neratinib) and Xeloda (capecitabine) reduced risk of disease progression or death (HR=0.76, p=0.006), improved 12-month PFS (28.8%, 88/307 vs 14.8%, 46/314) compared to lapatinib and capecitabine combination in patients with metastatic ERBB2 (HER2)-positive (amp/over exp) breast cancer who had 2 or more prior ERBB2 (HER2)-targeted therapies (J Clin Oncol 37, no. 15_suppl (May 20, 2019) 1002-1002; NCT01808573). | detail... |
| ERBB2 over exp | colorectal cancer | predicted - sensitive | Pertuzumab + Trastuzumab | Phase II | Actionable | In a Phase II trial (MyPathway), Herceptin (trastuzumab) and Perjeta (pertuzumab) combination treatment resulted in objective response in 38% (14/37, all partial response) and stable disease lasting over 120 days in 11% (4/37) of patients with colorectal cancer harboring ERBB2 (HER2) amplification or overexpression, with a median duration of response of 11 months (PMID: 29320312; NCT02091141). | 29320312 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Capecitabine + Trastuzumab | Guideline | Actionable | Herceptin (trastuzumab) combined with Xeloda (capecitabine) is included in guidelines as systemic therapy for patients with recurrent or metastatic hormone receptor-positive (ER and/or PR) or negative, ERBB2 (HER2)-positive breast cancer (NCCN.org). | detail... |
| ERBB2 over exp | lung non-small cell carcinoma | predicted - sensitive | Pertuzumab + Trastuzumab | Phase II | Actionable | In a Phase II trial (MyPathway), Herceptin (trastuzumab) and Perjeta (pertuzumab) combination treatment resulted in objective response in 13% (2/16, all partial response) and stable disease lasting over 120 days in 13% (2/16) of patients with non-small cell lung cancer harboring ERBB2 (HER2) amplification or overexpression (PMID: 29320312; NCT02091141). | 29320312 |
| ERBB2 over exp | pancreatic carcinoma | predicted - sensitive | HER2 CAR-T cells | Phase I | Actionable | In a Phase I trial, treatment with ERBB2 (HER2)-specific CAR-T cells demonstrated safety and preliminary activity in patients with biliary tract or pancreatic carcinoma with ERBB2 (HER2) over expression, resulting in partial response in one of 11 patients and stable disease in 5, and a median progression free survival of 4.8 months (PMID: 28710747; NCT01935843). | 28710747 |
| ERBB2 over exp | ovarian cancer | predicted - sensitive | Pertuzumab + Trastuzumab | Phase II | Actionable | In a Phase II trial (MyPathway), Herceptin (trastuzumab) and Perjeta (pertuzumab) combination treatment resulted in objective response in 13% (1/8, all partial response) of patients with ovarian cancer harboring ERBB2 (HER2) amplification or overexpression (PMID: 29320312; NCT02091141). | 29320312 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Trastuzumab + Vinorelbine | Guideline | Actionable | Herceptin (trastuzumab) combined with Navelbine (vinorelbine) is included in guidelines as systemic therapy for patients with recurrent or metastatic hormone receptor-positive (ER and/or PR) or negative, ERBB2 (HER2)-positive breast cancer (NCCN.org). | detail... |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Trastuzumab + Vinorelbine | Guideline | Actionable | The combination of Herceptin (trastuzumab) and Navelbine (vinorelbine) is included in guidelines as first-line therapy for patients with ERBB2 (HER2)-positive advanced breast cancer (PMID: 30032243; ESMO.org). | 30032243 detail... |
| ERBB2 over exp | breast cancer | sensitive | Trastuzumab-anns | FDA approved - On Companion Diagnostic | Actionable | In a Phase I trial that supported FDA approval, the Herceptin (trastuzumab) biosimilar Kanjinti (Trastuzumab-anns) demonstrated structure, function, and pharmacokinetic profile comparable to Herceptin (trastuzumab) (PMID: 28341959), thus supporting the extrapolation of data from the Phase III trial that supported the approval of Herceptin (trastuzumab) in Erbb2 (Her2) overexpressing breast cancer (PMID: 23801166) for approval of Kanjinti (Trastuzumab-anns) (FDA.gov). | detail... 23801166 28341959 detail... detail... |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Trastuzumab | Guideline | Actionable | Herceptin (trastuzumab) combined with a taxane, such as Taxotere (docetaxel) or Taxol (paclitaxel), is included in guidelines as neoadjuvant therapy for patients with ERBB2 (HER2)-positive early breast cancer or as first-line therapy for patients with ERBB2 (HER2)-positive advanced breast cancer (PMID: 31236598, PMID: 30032243; ESMO.org). | detail... 31236598 30032243 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Trastuzumab | FDA approved - On Companion Diagnostic | Actionable | Herceptin (trastuzumab) is FDA approved as an adjuvant treatment for ERBB2 (HER2)-overexpressing (or amplification) breast cancer patients and for metastatic ERBB2 (HER2)-overexpressing (or amplification) breast cancer patients as indicated by an FDA approved companion diagnostic (FDA.gov). | detail... detail... |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Ado-trastuzumab emtansine | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (KATHERINE) that supported FDA approval, treatment with Kadclya (trastuzumab emtansine) resulted in improved invasive disease-free survival (HR=0.50, p<0.001) compared to Herceptin (trastuzumab) in patients with ERBB2 (HER2)-positive early breast cancer who had residual invasive disease after taxane and trastuzumab-based neoadjuvant therapy (PMID: 30516102; NCT01772472). | detail... detail... 30516102 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Ado-trastuzumab emtansine | Guideline | Actionable | Kadcyla (ado-trastuzumab emtansine) is included in the guidelines for patients with ERBB2 (HER2)-positive advanced breast cancer who progressed through one line of Herceptin (trastuzumab)-based therapy or ERBB2 (HER2)-positive patients with early breast cancer (PMID: 31236598, PMID: 30032243; ESMO.org). | 31236598 detail... 30032243 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Ado-trastuzumab emtansine | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (EMILIA) that supported FDA approval, treatment with Kadclya (trastuzumab emtansine) improved median progression free survival (9.6 mo vs 6.4 mo) and overall survival (30.9 mo vs 25.1 mo) compared to Tykerb (lapatinib) combined with Xeloda (capecitabine) in patients with metastatic ERBB2 (HER2)-positive breast cancer (PMID: 24879797, PMID: 23020162; NCT00829166). | 24879797 detail... detail... 23020162 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Ado-trastuzumab emtansine | Guideline | Actionable | Kadcyla (ado-trastuzumab emtansine) is included in guidelines as systemic therapy for patients with recurrent or metastatic hormone receptor-positive (ER and/or PR) or negative, ERBB2 (HER2)-positive breast cancer (NCCN.org). | detail... |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | trastuzumab and hyaluronidase-oysk injection | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (HannaH) that supported FDA approval, Herceptin Hylecta (trastuzumab and hyaluronidase-oysk injection) treatment demonstrated safety and efficacy profile comparable to intravenous trastuzumab treatment, resulted in pathologic complete response in 45.4% (118/260) of patients with ERBB2 (HER2)-positive (IHC 3+ or ISH positive) breast cancer (PMID: 22884505; NCT00950300). | detail... detail... 22884505 |
| ERBB2 over exp | gastroesophageal adenocarcinoma | sensitive | Trastuzumab-anns | FDA approved - On Companion Diagnostic | Actionable | In a Phase I trial that supported FDA approval, the Herceptin (trastuzumab) biosimilar Kanjinti (Trastuzumab-anns) demonstrated structure, function, and pharmacokinetic profile comparable to Herceptin (trastuzumab) (PMID: 28341959), thus supporting the extrapolation of data from the Phase III trial that supported the approval of Herceptin (trastuzumab) in Erbb2 (Her2) overexpressing gastrioesophageal adenocarcinoma (PMID: 20728210; NCT01041404) for approval of Kanjinti (Trastuzumab-anns) (FDA.gov). | 20728210 detail... 28341959 detail... detail... |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Trastuzumab-anns | Phase III | Actionable | In a Phase III (LILAC) trial, Kanjinti (Trastuzumab-anns) treatment demonstrated safety and efficacy similar to Herceptin (trastuzumab) in neoadjuvant and adjuvant settings, resulted in a complete response in 48% (172/358) of patients with Erbb2 (Her2)-positive breast cancer, compared to 41% (137/338) in Herceptin (trastuzumab)-treated patients (PMID: 29880292; NCT01901146). | 29880292 |
| ERBB2 over exp | gastric adenocarcinoma | predicted - sensitive | Capecitabine + Lapatinib + Oxaliplatin | Phase II | Actionable | In a Phase II trial, Tykerb (lapatinib), Xeloda (capecitabine), and Eloxatin (oxaliplatin) combination treatment resulted in a disease control rate of 81.3% (26/32, 7 complete response, 15 partial response, 4 stable disease) in patients with Erbb2 (Her2)-positive (defined as IHC3+ or IHC 2+ with ERBB2 amplification) gastric adenocarcinoma (PMID: 29409051; NCT02015169). | 29409051 |
| ERBB2 over exp | salivary gland cancer | predicted - sensitive | Pertuzumab + Trastuzumab | Phase II | Actionable | In a Phase II trial (MyPathway), Herceptin (trastuzumab) and Perjeta (pertuzumab) combination treatment resulted in objective response in 80% (4/5, all partial response) of patients with salivary gland cancer harboring ERBB2 (HER2) amplification or overexpression (PMID: 29320312; NCT02091141). | 29320312 |
| ERBB2 over exp | stomach cancer | sensitive | Lapatinib | Preclinical | Actionable | In a preclinical study, Tykerb (lapatinib) inhibited growth of HER2-amplified and HER2-over expressing gastric cancer cell lines in culture (PMID: 18774637). | 18774637 |
| ERBB2 over exp | Her2-receptor positive breast cancer | predicted - sensitive | Margetuximab | Phase Ib/II | Actionable | In Phase I clinical trial, Margetuximab (MGAH22) displayed safety and had initial efficacy in patients with ERBB2 (HER2) positive breast cancer (J Clin Oncol 31, 2013 (suppl; abstr 3004)). | detail... |
| ERBB2 over exp | salivary gland carcinoma | predicted - sensitive | Pertuzumab + Trastuzumab | Phase II | Actionable | In a Phase II (MyPathway) trial, Perjeta (pertuzumab) and Herceptin (trastuzumab) combination therapy resulted in an objective response rate of 60% (9/15, 1 complete response, 8 partial responses) and a clinical benefit rate of 67% (10/15) in patients with advanced salivary gland carcinoma harboring ERBB2 (HER2) amplification or overexpression, with a median progression- free survival of 8.6 months, and a median overall survival of 20.4 months (PMID: 32067683; NCT02091141). | 32067683 |
| ERBB2 over exp | stomach cancer | sensitive | Ado-trastuzumab emtansine | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited tumor growth in human cell line xenograft models of gastric cancer with ERBB2 (HER2) amplification and over expression (PMID: 21458915). | 21458915 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | PF-05280014 | Preclinical | Actionable | In a preclinical study, PF-05280014 inhibited growth of ERBB2 (HER2)-over expressing breast cancer cells with activity comparable to Herceptin (trastuzumab) in culture (PMID: 25001079). | 25001079 |
| ERBB2 over exp | pancreatic cancer | predicted - sensitive | Pertuzumab + Trastuzumab | Phase II | Actionable | In a Phase II trial (MyPathway), Herceptin (trastuzumab) and Perjeta (pertuzumab) combination treatment resulted in objective response in 22% (2/9, all partial response) and stable disease lasting over 120 days in 11% (1/9) of patients with pancreatic cancer harboring ERBB2 (HER2) amplification or overexpression (PMID: 29320312; NCT02091141). | 29320312 |
| ERBB2 over exp | stomach cancer | sensitive | Tucatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Tukysa (tucatinib) inhibited proliferation of an ERBB2 (HER2) over expressing gastric cancer cell line in culture (Cancer Res April 15, 2010 70:3610). | detail... |
| ERBB2 over exp | gastric adenocarcinoma | sensitive | VS-5584 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, VS-5584 inhibited tumor growth in human gastric cancer cell line xenograft models overexpressing ERBB2 (HER2) (PMID: 23270925). | 23270925 |
| ERBB2 over exp | esophagus adenocarcinoma | sensitive | Trastuzumab | Guideline | Actionable | Herceptin (trastuzumab), in combination with first-line chemotherapy with fluoropyrimidine and cisplatin or other chemotherapy agents, but not anthracyclines, is included in guidelines for Erbb2 (Her2)-overexpressing metastatic esophageal adenocarcinoma patients (NCCN.org) | detail... |
| ERBB2 over exp | uterine cancer | no benefit | Pertuzumab + Trastuzumab | Phase II | Actionable | In a Phase II trial (MyPathway), Herceptin (trastuzumab) and Perjeta (pertuzumab) combination treatment resulted in no objective response (0/7) in patients with uterine cancer harboring ERBB2 (HER2) amplification or overexpression (PMID: 29320312; NCT02091141). | 29320312 |
| ERBB2 over exp | gastroesophageal junction adenocarcinoma | sensitive | S-222611 | Phase I | Actionable | In a Phase I trial, S-222611 resulted in a complete response in a gastric-esophageal junction cancer patient over expressing ERBB2 (HER2) and a partial response in a gastric cancer patient also over expressing ERBB2 (HER2) (J Clin Oncol 33, 2015 (suppl; abstr 2511)). | detail... |
| ERBB2 over exp | stomach cancer | sensitive | Trastuzumab + Varlitinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Varlitinib (ARRY-334543), in combination with Herceptin (trastuzumab), resulted in a 91% tumor growth inhibition and tumor regression in human cell line xenograft models of gastric cancer overexpressing ERBB2 (HER2) (Cancer Res January 15, 2009 69; 2150). | detail... |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Capecitabine + Trastuzumab + Tucatinib | Guideline | Actionable | Tukysa (tucatinib), Herceptin (trastuzumab), and Xeloda (capecitabine) combination therapy is included in guidelines as systemic therapy for patients with recurrent or metastatic hormone receptor-positive (ER and/or PR) or negative, ERBB2 (HER2)-positive breast cancer (NCCN.org). | detail... |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Capecitabine + Trastuzumab + Tucatinib | FDA approved | Actionable | In a Phase II trial (HER2CLIMB) that supported FDA approval, addition of Tukysa (tucatinib) to Herceptin (trastuzumab) and Xeloda (capecitabine) significantly improved progression-free survival at 1 year (PFS1) compared to placebo (33.1% vs 12.3%, HR=0.54, p<0.001) in patients with metastatic ERBB2 (HER2)-positive breast cancer who received prior HER2-targeted therapy, PFS1 was significantly improved (24.9% vs 0%, HR=0.48, p<0.001) in patients with brain metastasis (PMID: 31825569; NCT02614794). | detail... 31825569 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | NAX014 | Preclinical | Actionable | In a preclinical study, NAX014 induced cellular senescence, prevented tumor growth, and decreased tumor volume in a Her2 positive breast cancer mouse model (PMID: 26168818). | 26168818 |
| ERBB2 over exp | breast cancer | sensitive | KU004 | Preclinical | Actionable | In a preclinical study, KU004 inhibited growth and induced apoptosis in breast cancer cell lines over expressing ERBB2 in culture (PMID: 26437915). | 26437915 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Lapatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Tykerb (lapatinib) inhibited growth of HER2-over expressing breast carcinoma cell lines in culture (PMID: 27450453). | 27450453 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Carboplatin + Paclitaxel + Trastuzumab | Guideline | Actionable | Herceptin combined with Paraplatin (carboplatin) and Taxol (paclitaxel) is included in guidelines as systemic therapy for patients with recurrent or metastatic hormone receptor-positive (ER and/or PR) or negative, ERBB2 (HER2)-positive breast cancer (NCCN.org). | detail... |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Fam-trastuzumab deruxtecan-nxki | Guideline | Actionable | Enhertu (fam-trastuzumab deruxtecan-nxki) is included in guidelines as systemic therapy for patients with recurrent or metastatic hormone receptor-positive (ER and/or PR) or negative, ERBB2 (HER2)-positive breast cancer (NCCN.org). | detail... |
| ERBB2 over exp | biliary tract cancer | predicted - sensitive | HER2 CAR-T cells | Phase I | Actionable | In a Phase I trial, treatment with ERBB2 (HER2)-specific CAR-T cells demonstrated safety and preliminary activity in patients with biliary tract or pancreatic carcinoma with ERBB2 (HER2) over expression, resulting in partial response in one of 11 patients and stable disease in 5, and a median progression free survival of 4.8 months (PMID: 28710747; NCT01935843). | 28710747 |
| ERBB2 over exp | stomach cancer | sensitive | M802 | Preclinical - Cell culture | Actionable | In a preclinical study, M802 inhibited growth of a gastric cancer cell line expressing high levels of ERBB2 (HER2) in culture, and inhibited tumor growth in xenograft models (PMID: 31412896). | 31412896 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Paclitaxel + Pertuzumab + Trastuzumab | Guideline | Actionable | Perjeta (pertuzumab), Herceptin (trastuzumab), and Taxol (paclitaxel) therapy is included in the guidelines as systemic therapy for patients with recurrent or metastatic hormone receptor-positive (ER and/or PR) or negative, ERBB2 (HER2) receptor-positive breast cancer (NCCN.org). | detail... |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Capecitabine + Lapatinib | Guideline | Actionable | Tykerb (lapatinib) combined with Xeloda (capecitabine) is included in guidelines as systemic therapy for patients with recurrent or metastatic hormone receptor-positive (ER and/or PR) or negative, ERBB2 (HER2)-positive breast cancer (NCCN.org). | detail... |
| ERBB2 over exp | stomach cancer | sensitive | MM-111 + Paclitaxel + Trastuzumab | Preclinical - Cell line xenograft | Actionable | In a preclinical study, MM-111, in combination with Herceptin (trastuzumab) and Taxol (paclitaxel), resulted in a synergistic effect thereby inhibiting ErbB2 in ERBB2 (HER2) over expressing gastric cancer cell line xenograft models (J Clin Oncol 31, 2013 (suppl 4; abstr 48)). | detail... |
| ERBB2 over exp | stomach cancer | predicted - sensitive | MM-302 | Preclinical | Actionable | In a preclinical study, ERBB2 (HER2) over expressing gastric cancer xenograft models demonstrated anti-tumor activity when treated with MM-302 (Cancer Res December 15, 2010 70; P3-14-09). | detail... |
| ERBB2 over exp | stomach cancer | sensitive | Varlitinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Varlitinib (ARRY-334543) resulted in a 74% tumor growth inhibition and tumor regression in 88% (7/8) of human cell line xenograft models of gastric cancer overexpressing ERBB2 (HER2) (Cancer Res January 15, 2009 69; 2150). | detail... |
| ERBB2 over exp | breast cancer | sensitive | ZW49 | Preclinical - Pdx | Actionable | In a preclinical study, ZW49 treatment induced tumor regression in a patient-derived xenograft (PDX) model of breast cancer overexpressing ERBB2 (HER2) (Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-13). | detail... |
| ERBB2 over exp | stomach cancer | sensitive | TAK-285 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TAK-285 inhibited tumor growth in gastric cancer cell line xenograft models over expressing ERBB2 (HER2) (PMID: 23983820). | 23983820 |
| ERBB2 over exp | stomach cancer | sensitive | TAK-285 | Preclinical | Actionable | In a preclinical study, the N87 gastric cancer cell line, which has been demonstrated to have ERBB2 (HER2) amplification and over expression, was sensitive to TAK-285, inhibiting phosphorylation of ERBB2 (HER2) and ERBB3 (HER3) (PMID: 25594012, PMID: 18441328). | 18441328 25594012 |
| ERBB2 over exp | urinary bladder cancer | predicted - sensitive | Pertuzumab + Trastuzumab | Phase II | Actionable | In a Phase II trial (MyPathway), Herceptin (trastuzumab) and Perjeta (pertuzumab) combination treatment resulted in objective response in 33% (3/9, 1 complete response, 1 partial response) and stable disease lasting over 120 days in 22% (2/9) of patients with bladder cancer harboring ERBB2 (HER2) amplification or overexpression (PMID: 29320312; NCT02091141). | 29320312 |
| ERBB2 over exp | breast cancer | sensitive | AV-412 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AV-412 inhibited growth of ERBB2 (HER2)-over expressing breast cancer cell lines in culture, and inhibited tumor growth in a ERBB2 (HER2)-over expressing breast cancer cell line xenograft model (PMID: 17888033). | 17888033 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Docetaxel + Pertuzumab + Trastuzumab | Guideline | Actionable | Perjeta (pertuzumab), Herceptin (trastuzumab), and Taxotere (docetaxel) therapy is included in the guidelines as systemic therapy for patients with recurrent or metastatic hormone receptor-positive (ER and/or PR) or negative, ERBB2 (HER2)-positive breast cancer (NCCN.org). | detail... |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Docetaxel + Pertuzumab + Trastuzumab | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (CLEOPATRA) that supported FDA approval, treatment with Perjeta (pertuzumab), combined with Herceptin (trastuzumab) and Taxotere (docetaxel), improved median progression free survival to 18.5 months compared to 12.4 months with placebo plus Herceptin (trastuzumab) and Taxotere (docetaxel) in patients with ERBB2 (HER2)-positive (overexpression and amplification) metastatic breast cancer (PMID: 23801166). | detail... 23801166 detail... |
| ERBB2 over exp | stomach cancer | sensitive | MBS301 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, MBS301 inhibited proliferation of a gastric cancer cell line expressing high levels of ERBB2 (HER2) in culture, and inhibited tumor growth in xenograft models (PMID: 30081724). | 30081724 |
| ERBB2 over exp | stomach cancer | sensitive | HER2 CAR-T cells | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ERBB2 (HER2)-specific CAR-T cells induced cell death in ERBB2 (HER2)-over expressing gastric cancer cell lines in culture, and inhibited tumor growth and improved survival in a ERBB2 (HER2)-over expressing gastric cancer cell line xenograft model (PMID: 28284008). | 28284008 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Pertuzumab + Trastuzumab | Guideline | Actionable | The combination of Herceptin (trastuzumab) and Perjeta (pertuzumab) with a taxane, such as Taxotere (docetaxel) or Taxol (palictaxel), is included in guidelines for patients with ERBB2 (HER2)-positive early breast cancer patients or advanced breast cancer (PMID: 31236598, PMID: 30032243; ESMO.org). | 31236598 detail... 30032243 |
| ERBB2 over exp | breast cancer | sensitive | MM-302 + Trastuzumab | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination of MM-302 and Herceptin (trastuzumab) synergistically inhibited tumor growth in cell line xenograft models of Erbb2 (Her2)-over expressing breast cancer (PMID: 26759238). | 26759238 |
| ERBB2 over exp | breast cancer | sensitive | M802 | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with M802 increased apoptosis and inhibited growth of breast cancer cell lines expressing high levels of ERBB2 (HER2) in culture (PMID: 31412896). | 31412896 |
| ERBB2 over exp | stomach cancer | sensitive | KU004 | Preclinical | Actionable | In a preclinical study, KU004 inhibited growth and induced apoptosis in gastric cancer cell lines over expressing ERBB2 in culture and suppressed growth in a dose dependent manner in xenograft models (PMID: 26437915). | 26437915 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Neratinib | Guideline | Actionable | Nerlynx (neratinib) is included in guidelines for patients with high-risk ERBB2 (HER2)-positive early breast cancer (PMID: 31236598; ESMO.org). | 31236598 detail... |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | Neratinib | FDA approved | Actionable | In a Phase III trial that supported FDA approval, ERBB2 (HER2)-positive (overexpressing and/or amplification) breast cancer patients previously treated with Herceptin (trastuzumab) demonstrated a significantly greater two year invasive disease-free survival rate (93.9%) when treated with Nerlynx (neratinib) compared to the rate (91.6%) in those patients treated with placebo (PMID: 26874901; NCT00878709). | 26874901 detail... |
| ERBB2 over exp | gastroesophageal junction adenocarcinoma | sensitive | Trastuzumab | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (ToGA) that supported FDA approval, patients with either gastric cancer or gastroesophageal junction adenocarcinoma with ERBB2 (HER2) overexpression or ERBB2 (HER2) amplification had increased overall survival (13.8 mo vs 11.1 mo) when treated with Herceptin (trastuzumab) in combination with chemotherapy compared to chemotherapy alone (PMID: 20728210; NCT01041404). | 20728210 detail... detail... |
| ERBB2 over exp | gastroesophageal junction adenocarcinoma | sensitive | Trastuzumab | Guideline | Actionable | Herceptin (trastuzumab), in combination with fluoropyrimidine and cisplatin, or other chemotherapy agents, but not anthracyclines, is included in guidelines for Erbb2 (Her2)-overexpressing metastatic esophagogastric junction adenocarcinoma patients (NCCN.org) | detail... |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | CUDC-101 | Phase I | Actionable | In a Phase I clinical trial, a breast cancer patient with ERBB2 (HER2) over expression that had progressed on Herceptin (trastuzumab) demonstrated stable disease for more than 12 weeks following treatment with CUDC-101 (PMID: 25107918). | 25107918 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | ADXS31-164 | Preclinical | Actionable | In a preclinical study, ADXS31-164 prevented development of spontaneous mammary tumors in Erbb2 (Her2)-over expressing transgenic animal models (PMID: 20725099). | 20725099 |
| ERBB2 over exp | Her2-receptor positive breast cancer | sensitive | TAK-285 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TAK-285 inhibited growth of breast cancer cell line harboring ERBB2 (HER2) over expression in culture and in cell line xenograft models (PMID: 23983820). | 23983820 |
| ERBB2 over exp | stomach cancer | sensitive | MM-302 + Trastuzumab | Preclinical - Cell line xenograft | Actionable | In a preclinical study, combination of MM-302 and Herceptin (trastuzumab) resulted in improved tumor growth inhibition in cell line xenograft models of Erbb2 (Her2)-over expressing gastric cancer (PMID: 26759238). | 26759238 |
| ERBB2 over exp | biliary tract cancer | predicted - sensitive | Pertuzumab + Trastuzumab | Phase II | Actionable | In a Phase II trial (MyPathway), Herceptin (trastuzumab) and Perjeta (pertuzumab) combination treatment resulted in objective response in 29% (2/7, all partial response) and stable disease lasting over 120 days in 38% (3/7) of patients with biliary cancer harboring ERBB2 (HER2) amplification or overexpression (PMID: 29320312; NCT02091141). | 29320312 |
| ERBB2 over exp | stomach cancer | sensitive | CDX-3379 | Preclinical | Actionable | In a preclinical study, CDX-3379 (KTN3379) inhibited tumor growth by 43% in N87 gastric cancer xenograft model, which has been demonstrated to have ERBB2 (HER2) amplification and overexpression (AACR; 2015. Abstract nr 1558, PMID: 18441328). | detail... 18441328 |
| ERBB2 over exp | gastric adenocarcinoma | sensitive | Trastuzumab-anns | FDA approved - On Companion Diagnostic | Actionable | In a Phase I trial that supported FDA approval, the Herceptin (trastuzumab) biosimilar Kanjinti (Trastuzumab-anns) demonstrated structure, function, and pharmacokinetic profile comparable to Herceptin (trastuzumab) (PMID: 28341959), thus supporting the extrapolation of data from the Phase III trial that supported the approval of Herceptin (trastuzumab) in Erbb2 (Her2) overexpressing gastric adenocarcinoma (PMID: 20728210; NCT01041404) for approval of Kanjinti (Trastuzumab-anns) (FDA.gov). | 20728210 28341959 detail... detail... detail... |
| ERBB2 over exp | cholangiocarcinoma | predicted - sensitive | HER2 CAR-T cells | Phase I | Actionable | In a Phase I trial, a patient with perihilar cholangiocarcinoma over expressing ERBB2 achieved a partial response and progression-free survival for 4.5 months following treatment with ERBB2 (HER2)-specific CAR-T cells (PMID: 28710747, NCT01935843). | 28710747 |
| ERBB2 over exp | gastric adenocarcinoma | sensitive | Trastuzumab | FDA approved - On Companion Diagnostic | Actionable | In a Phase III trial (ToGA) that supported FDA approval, patients with either gastric or gastroesophageal junction adenocarcinoma with ERBB2 (HER2) overexpression or ERBB2 (HER2) amplification had increased overall survival (13.8 mo vs 11.1 mo) when treated with Herceptin (trastuzumab) in combination with chemotherapy compared to chemotherapy alone (PMID: 20728210; NCT01041404). | 20728210 detail... detail... |
| ERBB2 over exp | gastric adenocarcinoma | sensitive | Trastuzumab | Guideline | Actionable | Herceptin (trastuzumab) in combination with fluoropyrimidine and cisplatin (category 1) or other platinum agents (category 2A), but not anthracyclines, is included in guidelines as first-line therapy for Erbb2 (Her2)-overexpressing metastatic gastric adenocarcinoma patients (NCCN.org) | detail... |
| ERBB2 over exp | Advanced Solid Tumor | predicted - sensitive | Pertuzumab + Trastuzumab | Phase II | Actionable | In a Phase II trial (MyPathway), Herceptin (trastuzumab) and Perjeta (pertuzumab) combination treatment resulted in objective response in 26% (30/114, 2 complete response, 28 partial response) and stable disease lasting over 120 days in 14% (16/114) of patients with advanced solid tumors harboring ERBB2 (HER2) amplification or overexpression (PMID: 29320312; NCT02091141). | 29320312 |
| ERBB2 over exp PIK3CA H1047R | Her2-receptor positive breast cancer | resistant | Pertuzumab + Trastuzumab | Preclinical | Actionable | In a preclinical study, a mouse breast cancer model with ERBB2 (HER2) over-expression that also expressed the PIK3CA H1047R mutation showed resistance to the combination of Heceptin (trastuzumab) and Perjeta (pertuzumab) (PMID: 23940356). | 23940356 |
| ERBB2 over exp PIK3CA H1047R | Her2-receptor positive breast cancer | sensitive | Buparlisib + Pertuzumab + Trastuzumab | Preclinical | Actionable | In a preclinical study, the combination of Buparlisib (BKM120), Herceptin (trastuzumab), and Perjeta (pertuzumab) inhibited tumor growth in mouse models of ERBB2 (HER2)-over expressing breast cancer expressing PIK3CA H1047R, with improved efficacy over Buparlisib (BKM120) alone (PMID: 23940356). | 23940356 |
| ERBB2 over exp PIK3CA H1047R | Her2-receptor positive breast cancer | resistant | Trastuzumab | Preclinical | Actionable | In a preclinical study, mouse breast cancer models over expressing ERBB2 (HER2) and expressing PIK3CA H1047R were resistant to Herceptin (trastuzumab) (PMID: 23940356). | 23940356 |
| ERBB2 over exp PIK3CA H1047R | Her2-receptor positive breast cancer | sensitive | Bevacizumab + Buparlisib | Preclinical | Actionable | In a preclinical study, treatment with Buparlisib (BKM120) resulted in decreased tumor growth, but not tumor regression, in mouse models of ERBB2 (HER2)-over expressing breast cancer expressing PIK3CA H1047R (PMID: 23940356). | 23940356 |
| ERBB2 over exp PIK3CA H1047R | Her2-receptor positive breast cancer | no benefit | Buparlisib + Lapatinib + Trastuzumab | Preclinical | Actionable | In a preclinical study, the combination of Buparlisib (BKM120), Herceptin (trastuzumab), and Tykerb (lapatinib) inhibited tumor growth in mouse models of ERBB2 (HER2)-over expressing breast cancer expressing PIK3CA H1047R, but efficacy was not significantly improved over Buparlisib (BKM120) alone (PMID: 23940356). | 23940356 |
| ERBB2 over exp PIK3CA H1047R | Her2-receptor positive breast cancer | resistant | Lapatinib + Trastuzumab | Preclinical | Actionable | In a preclinical study, a mouse breast cancer model with mammary ERBB2 (HER2) over-expression that also expressed the PIK3CA H1047R mutation showed resistance to the combination of Herceptin (trastuzumab) and Tykerb (lapatinib) (PMID: 23940356). | 23940356 |
| ERBB2 over exp PIK3CA H1047R | stomach cancer | predicted - resistant | Trastuzumab | Clinical Study - Cohort | Actionable | In a clinical study (AMNESIA-1), assessment of pre-treatment tumor samples from ERBB2 (HER2)-positive gastric or gastroesophageal cancer patients (defined as HER2 IHC 3+ or HER2 IHC 2+/ISH+) identified PIK3CA mutations in 15% (3/20) of patients demonstrating primary resistance to Herceptin (trastuzumab), including 1 patient harboring PIK3CA H1047R (PMID: 29208673). | 29208673 |
| ERBB2 over exp PIK3CA H1047R | Her2-receptor positive breast cancer | sensitive | Buparlisib + Trastuzumab | Preclinical | Actionable | In a preclinical study, the combination of Herceptin (trastuzumab) and Buparlisib (BKM120) inhibited tumor growth in mouse ERBB2 (HER2)-over expressing breast cancer models expressing PIK3CA H1047R, with moderate efficacy over Buparlisib (BKM120) alone (PMID: 23940356). | 23940356 |
| ERBB2 over exp PIK3CA H1047R SRC over exp | urinary bladder cancer | no benefit | Ponatinib | Preclinical - Pdx | Actionable | In a preclinical study, treatment with Iclusig (ponatinib) was not effective in inhibiting tumor growth in a patient-derived xenograft (PDX) model of bladder cancer with SRC over expression, which also over expressed ERBB2 (HER2) and harbored PIK3CA H1047R (PMID: 26270481). | 26270481 |
| ERBB2 over exp PIK3CA H1047R SRC over exp | urinary bladder cancer | no benefit | Lapatinib | Preclinical - Pdx | Actionable | In a preclinical study, treatment with Tykerb (lapatinib) was not effective in inhibiting tumor growth in a patient-derived xenograft (PDX) model of bladder cancer with ERBB2 (HER2) over expression, which also over expressed SRC and harbored PIK3CA H1047R (PMID: 26270481). | 26270481 |
| ERBB2 amp ERBB2 over exp | stomach cancer | sensitive | Ado-trastuzumab emtansine | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Kadcyla (trastuzumab emtansine) inhibited tumor growth in human cell line xenograft models of gastric cancer with ERBB2 (HER2) amplification and over expression (PMID: 21458915). | 21458915 |
| ERBB2 amp ERBB2 over exp | stomach cancer | sensitive | Afatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Gilotrif (afatinib) induced tumor regression in a gastric cancer cell line xenograft model with HER2 (ERBB2) amplification and over expression (PMID: 23578997). | 23578997 |
| ERBB2 over exp PIK3CA mut | Her2-receptor positive breast cancer | sensitive | PKI-179 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PKI-179 inhibited growth of breast cancer cells harboring PIK3CA mutations and ERBB2 (HER2) over expression in culture and cell line xenograft models (PMID: 20797855). | 20797855 |
| ERBB2 over exp PIK3CA mut | breast cancer | sensitive | Miransertib + Paclitaxel | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a breast cancer xenograft model with ERBB2 (HER2) over expression and harboring a PIK3CA mutation was sensitive to the combination treatment of Miransertib (ARQ092) and Taxol (paclitaxel), demonstrating greater inhibition of tumor growth when compared to treatment with either agent alone (PMID: 26469692). | 26469692 |
| ERBB2 over exp PIK3CA mut | breast cancer | sensitive | Miransertib + Trastuzumab | Preclinical - Cell line xenograft | Actionable | In a preclinical study, a breast cancer xenograft model with ERBB2 (HER2) over expression and harboring a PIK3CA mutation was sensitive to the combination treatment of Miransertib (ARQ092) and Herceptin (trastuzumab), demonstrating greater inhibition of tumor growth when compared to treatment with either agent alone (PMID: 26469692). | 26469692 |
| ERBB2 over exp PIK3CA N345T | stomach cancer | predicted - resistant | Trastuzumab | Clinical Study - Cohort | Actionable | In a clinical study (AMNESIA-1), assessment of pre-treatment tumor samples from ERBB2 (HER2)-positive gastric or gastroesophageal cancer patients (defined as HER2 IHC 3+ or HER2 IHC 2+/ISH+) identified PIK3CA mutations in 15% (3/20) of patients demonstrating primary resistance to Herceptin (trastuzumab), including 1 patient harboring PIK3CA N345T (PMID: 29208673). | 29208673 |
| ERBB2 over exp PIK3CA H1047L | stomach cancer | predicted - resistant | Trastuzumab | Clinical Study - Cohort | Actionable | In a clinical study (AMNESIA-1), assessment of pre-treatment tumor samples from ERBB2 (HER2)-positive gastric or gastroesophageal cancer patients (defined as HER2 IHC 3+ or HER2 IHC 2+/ISH+) identified PIK3CA mutations in 15% (3/20) of patients demonstrating primary resistance to Herceptin (trastuzumab), including 1 patient harboring PIK3CA H1047L (PMID: 29208673). | 29208673 |
| ERBB2 over exp PIK3CA act mut | Her2-receptor positive breast cancer | decreased response | Poziotinib | Phase II | Actionable | In a Phase II trial, the presence of PIK3CA activating mutations including E542X, E545X, and H1047X correlated with shorter progression-free survival (2.66 months) compared to PIK3CA wild-type or other mutations (4.24 month, HR=1.68, p=0.033) in patients with metastatic Erbb2 (Her2)-positive (amplification or overexpression) breast cancer treated with Poziotinib (HM781-36B) (PMID: 30720867, NCT02418689). | 30720867 |
| ERBB2 over exp PIK3CA E542X | Her2-receptor positive breast cancer | decreased response | Poziotinib | Phase II | Actionable | In a Phase II trial, the presence of PIK3CA activating mutations including E542X, E545X, and H1047X correlated with shorter progression-free survival (2.66 months) compared to PIK3CA wild-type or other mutations (4.24 month, HR=1.68, p=0.033) in patients with metastatic Erbb2 (Her2)-positive (amplification or overexpression) breast cancer treated with Poziotinib (HM781-36B) (PMID: 30720867, NCT02418689). | 30720867 |
| ERBB2 over exp PIK3CA E545X | Her2-receptor positive breast cancer | decreased response | Poziotinib | Phase II | Actionable | In a Phase II trial, the presence of PIK3CA activating mutations including E542X, E545X, and H1047X correlated with shorter progression-free survival (2.66 months) compared to PIK3CA wild-type or other mutations (4.24 month, HR=1.68, p=0.033) in patients with metastatic Erbb2 (Her2)-positive (amplification or overexpression) breast cancer treated with Poziotinib (HM781-36B) (PMID: 30720867, NCT02418689). | 30720867 |
| ERBB2 over exp PIK3CA H1047X | Her2-receptor positive breast cancer | decreased response | Poziotinib | Phase II | Actionable | In a Phase II trial, the presence of PIK3CA activating mutations including E542X, E545X, and H1047X correlated with shorter progression-free survival (2.66 months) compared to PIK3CA wild-type or other mutations (4.24 month, HR=1.68, p=0.033) in patients with metastatic Erbb2 (Her2)-positive (amplification or overexpression) breast cancer treated with Poziotinib (HM781-36B) (PMID: 30720867, NCT02418689). | 30720867 |