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Gene ERBB2
Variant amp
Impact List none
Protein Effect no effect
Gene Variant Descriptions ERBB2 (HER2) amplification indicates an increased number of copies of the ERBB2 (HER2) gene. However, the mechanism causing the increase is unspecified.
Associated Drug Resistance

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No Variant Reference Transcript is Available.
No transcript is Available.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ERBB2 amp lung adenocarcinoma no benefit Dacomitinib Phase II Actionable In a Phase II trial, Vizimpro (dacomitinib) treatment resulted in an overall response rate of 0% (0/4) in patients with lung adenocarcinoma harboring ERBB2 (HER2) amplification (PMID: 25899785; NCT00818441). 25899785
ERBB2 amp 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 ERBB2 (HER2)-positive patients with early breast cancer patients or advanced breast cancer (PMID: 31236598, PMID: 30032243; ESMO.org). detail... 31236598 30032243
ERBB2 amp 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 amp Her2-receptor positive breast cancer sensitive Neratinib Guideline Actionable Nerlynx (neratinib) is included in guidelines for ERBB2 (HER2)-positive patients with high-risk early breast cancer (PMID: 31236598; ESMO.org). detail... 31236598
ERBB2 amp 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 amp Her2-receptor positive breast cancer sensitive Trastuzumab Clinical Study - Meta-analysis Actionable In a meta-analysis, breast cancer patients with >12 copies of ERBB2 (HER2) had a better response to Herceptin (trastuzumab) than patients with 6-12 copies of ERBB2 (HER2) (PMID: 24691421). 24691421
ERBB2 amp 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 ERBB2 (HER2)-positive patients with early breast cancer or as first-line therapy for ERBB2 (HER2)-positive patients with advanced breast cancer (PMID: 31236598, PMID: 30032243; ESMO.org). 31236598 detail... 30032243
ERBB2 amp 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 amp 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 amp breast cancer sensitive LJM716 + Trastuzumab Preclinical - Cell line xenograft Actionable In a preclinical study, breast cancer cell line xenograft models harboring ERBB2 (HER2) amplification were sensitive to the combination of Herceptin (trastuzumab) and LJM716, resulting in a delay of brain lesion growth and improved survival (PMID: 28539475). 28539475
ERBB2 amp 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 amp 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 amp vulva squamous cell carcinoma sensitive Depatuxizumab mafodotin Preclinical - Cell line xenograft Actionable In a preclinical study, ABT-414 demonstrated cytoxicity against a EGFR-amplified vulvar epidermoid carcinoma cell line in culture and induced tumor regression in EGFR-amplified vulvar epidermoid carcinoma cell line xenograft models (PMID: 26846818). 26846818
ERBB2 amp stomach cancer predicted - sensitive Fluorouracil + Oxaliplatin + Trastuzumab Case Reports/Case Series Actionable In a Phase II clinical trial, a gastric cancer patient with ERBB2 (HER2) amplification demonstrated a response for 24 months when treated with the combination of Adrucil (fluorouracil), Eloxatin (oxaliplatin), and Herceptin (trastuzumab) (PMID: 30463996; NCT01522768). 30463996
ERBB2 amp Her2-receptor positive breast cancer sensitive Palbociclib + Trastuzumab Preclinical Actionable In a preclinical study, the combination of Ibrance (palbociclib) and Herceptin (trastuzumab) worked synergistically to inhibit growth of ERBB2 (HER2)-amplified breast cancer cells in culture (PMID: 19874578). 19874578
ERBB2 amp colorectal cancer resistant Trastuzumab Preclinical Actionable In a preclinical study, colorectal cancer tumorgrafts with ERBB2 (HER2) amplification demonstrated resistance to Herceptin (trastuzumab) treatment in animal models (PMID: 26296355). 26296355
ERBB2 amp breast cancer sensitive CYH33 Preclinical - Cell culture Actionable In a preclinical study, breast cancer cell lines harboring ERBB2 (HER2) amplification demonstrated increased sensitivity to CYH33 compared to cells with normal ERBB2 (HER2) expression in culture (p<0.05) (PMID: 30003928). 30003928
ERBB2 amp lung cancer sensitive Lapatinib Preclinical - Cell culture Actionable In a preclinical study, Tykerb (lapatinib) treatment reduced viability of a lung cancer cell line harboring an ERBB2 (HER2) amplification in culture (PMID: 30674502). 30674502
ERBB2 amp 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 amp 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 ERBB2 (HER2)-positive patients with advanced breast cancer (PMID: 30032243; ESMO.org). 30032243 detail...
ERBB2 amp colorectal cancer sensitive Cetuximab + Lapatinib Preclinical - Pdx Actionable In a preclinical study, the combination of Erbitux (cetuximab) and Tykerb (lapatinib) induced tumor regression in patient-derived xenograft (PDX) models of colorectal cancer with ERBB2 (HER2) amplification (PMID: 22586653). 22586653
ERBB2 amp 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 amp 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 amp urinary bladder cancer sensitive Afatinib Phase II Actionable In a Phase II clinical trial, patients with ERBB2 (HER2) amplified urothelial carcinoma had improved progression free survival when treated with Gilotrif (afatinib), and median PFS was 6.6 months for patients with ERBB2 or ERBB3 alterations relative to 1.4 months for patients lacking alterations (PMID: 27044931). 27044931
ERBB2 amp Her2-receptor positive breast cancer sensitive CDX-3379 + Trastuzumab Preclinical Actionable In a preclinical study, the combination of Herceptin (trastuzumab) and CDX-3379 (KTN3379) inhibited tumor growth in xenograft models of ERBB2 (HER2)-amplified breast cancer, with increased efficacy compared to KTN3379 alone (PMID: 26880266). 26880266
ERBB2 amp 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 amp Her2-receptor positive breast cancer predicted - sensitive BGB-283 Preclinical - Cell culture Actionable In a preclinical study, BGB-283 inhibited proliferation of ERBB2 (HER2) amplified breast cancer cells in culture (PMID: 26208524). 26208524
ERBB2 amp breast cancer sensitive Dacomitinib Preclinical Actionable In a preclinical study, Vizimpro (dacomitinib) was more effective in preventing proliferation in ERBB2 (HER2) amplified breast cancer cells than in wild-type ERBB2 (HER2) breast cancer cells (PMID: 22761403). 22761403
ERBB2 amp parotid gland cancer predicted - sensitive Ado-trastuzumab emtansine Phase II Actionable In a Phase II (MATCH) trial, Kadcyla (trastuzumab emtansine) treatment resulted in partial response in a patient with ERBB2 (HER2) amplified salivary duct carcinoma of the parotid gland and a patient with ERBB2 (HER2) amplified squamous cell carcinoma of the parotid gland (J Clin Oncol 36, 2018 (suppl; abstr 100); NCT02465060). detail...
ERBB2 amp uterine corpus serous adenocarcinoma sensitive Neratinib Preclinical - Cell culture Actionable In a preclinical study, a uterine serous carcinoma cell line harboring ERBB2 (HER2) amplification demonstrated sensitivity to treatment with Nerlynx (neratinib) in culture, resulting in inhibition of cell growth (PMID: 26333383). 26333383
ERBB2 amp stomach cancer sensitive Poziotinib Preclinical Actionable In a preclinical study, Poziotinib suppressed cell growth, decreased phosphorylation of downstream signaling molecules, and induced apoptosis of human gastric cancer cells harboring ERBB2 (HER2) amplification (PMID: 21306821). 21306821
ERBB2 amp stomach cancer sensitive Trastuzumab Preclinical - Cell line xenograft Actionable In a preclinical study, Herceptin (trastuzumab) inhibited tumor growth in human cell line xenograft models of gastric cancer with ERBB2 (HER2) amplification (PMID: 26296355). 26296355
ERBB2 amp duodenum adenocarcinoma predicted - sensitive Fluorouracil + Leucovorin + Oxaliplatin + Trastuzumab Case Reports/Case Series Actionable In a clinical case study, a patient with duodenal adenocarcinoma harboring ERBB2 (HER2) amplification demonstrated a complete pathologic response after treatment with a combination of Herceptin (trastuzumab), Adrucil (fluorouracil), Wellcovorin (leucovorin), and Eloxatin (oxaliplatin) (PMID: 28784859). 28784859
ERBB2 amp stomach cancer predicted - sensitive Afatinib + Trastuzumab Case Reports/Case Series Actionable In a Phase II clinical trial, a gastric cancer patient with ERBB2 (HER2) amplification who progressed on previous therapy demonstrated a 22% regression in a metastatic site when treated with a combination of Gilotrif (afatinib) and Herceptin (trastuzumab) (PMID: 30463996; NCT01522768). 30463996
ERBB2 amp lung squamous cell carcinoma resistant Gefitinib Preclinical Actionable In a preclinical study, a lung squamous cell carcinoma cell line with ERBB2 (HER2) amplification demonstrated resistance to treatment with Iressa (gefitinib) in culture (PMID: 26545934). 26545934
ERBB2 amp breast cancer predicted - sensitive Neratinib + Temsirolimus Phase I Actionable In a Phase I clinical trial, Nerlynx (neratinib) administered with Torisel (temsirolimus) was tolerable and demonstrated antitumor activity in ERBB2 (HER2)-amplified breast cancer resistant to (Herceptin) trastuzumab (PMID: 24323026). 24323026
ERBB2 amp 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). detail... 20728210 detail...
ERBB2 amp colorectal cancer sensitive Lapatinib + Trastuzumab Preclinical - Pdx Actionable In a preclinical study, the combination of Herceptin (trastuzumab) and Tykerb (lapatinib) treatment induced tumor regression in patient-derived colorectal cancer tumorgraft models harboring ERBB2 (HER2) amplification (PMID: 26296355). 26296355
ERBB2 amp 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 amp colorectal adenocarcinoma predicted - sensitive Ado-trastuzumab emtansine Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic colorectal adenocarcinoma harboring ERBB2 (HER2) amplification demonstrated clinical benefit with stable disease in the primary tumor for 7 months following treatment with Kadcyla (trastuzumab emtansine) (PMID: 28040715). 28040715
ERBB2 amp stomach cancer sensitive Lapatinib + Trastuzumab Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Herceptin (trastuzumab) and Tykerb (lapatinib) treatment induced tumor regression in ERBB2 (HER2)-amplified cell line xenograft models of gastric cancer (PMID: 26296355). 26296355
ERBB2 amp colorectal cancer no benefit Pertuzumab Preclinical - Pdx Actionable In a preclinical study, Perjeta (pertuzumab) did not inhibit tumor growth in patient-derived xenograft (PDX) models of ERBB2 (HER2)-amplified colorectal cancer (PMID: 22586653). 22586653
ERBB2 amp 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 amp breast cancer decreased response Lapatinib Preclinical - Cell culture Actionable In a preclinical study, ERBB2 (HER2) amplified breast cancer cells treated with Tykerb (lapatinib) demonstrated decreased phosphorylation of Erbb2 (her2) and Akt, however, after 4-8 hours, Akt-driven Rictor showed upregulation, thereby resulting in a decreased treatment response (PMID: 27197158). 27197158
ERBB2 amp colorectal cancer sensitive Lapatinib + Pertuzumab Preclinical - Pdx Actionable In a preclinical study, the combination of Perjeta (pertuzumab) and Tykerb (lapatinib) induced tumor regression in patient-derived xenograft (PDX) models of colorectal cancer with ERBB2 (HER2) amplification (PMID: 22586653). 22586653
ERBB2 amp breast cancer sensitive Neratinib + Pertuzumab Preclinical - Cell line xenograft Actionable In a preclinical study, breast cancer cell line xenograft models harboring ERBB2 (HER2) amplification were sensitive to the combination of Perjeta (pertuzumab) and Nerlynx (neratinib), resulting in a delay of brain lesion growth and improved survival (PMID: 28539475). 28539475
ERBB2 amp breast cancer sensitive Buparlisib Preclinical - Cell line xenograft Actionable In a preclinical study, a breast cancer cell line xenograft model harboring ERBB2 (HER2) amplification demonstrated tumor regression within the mammary fat pad when treated with Buparlisib (BKM120) (PMID: 28539475). 28539475
ERBB2 amp Her2-receptor positive breast cancer sensitive CDX-3379 Preclinical Actionable In a preclinical study, CDX-3379 (KTN3379) inhibited tumor growth in xenograft models of ERBB2 (HER2)-amplified breast cancer (PMID: 26880266). 26880266
ERBB2 amp Her2-receptor positive breast cancer sensitive Lapatinib + S63845 Preclinical - Cell culture Actionable In a preclinical study, the combination of Tykerb (lapatinib) and S63845 demonstrated synergy in an ERBB2 (HER2)-amplified breast cancer cell line in culture, resulting in decreased cell viability (PMID: 28768804). 28768804
ERBB2 amp Her2-receptor positive breast cancer predicted - sensitive KRIBB11 + MK2206 Preclinical - Cell culture Actionable In a preclinical study, MK-2206 and KRIBB11 synergistically inhibited growth of ERBB2 (HER2)-amplified breast cancer cell lines in culture (PMID: 28598816). 28598816
ERBB2 amp 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 amp acral lentiginous melanoma sensitive Ado-trastuzumab emtansine Case Reports/Case Series Actionable In a clinical case study, Kadcyla (trastuzumab emtansine) treatment resulted in complete radiographic response that lasted over 28 months in a patient with acral melanoma harboring ERBB2 (HER2) amplification (26-fold) that was resistant to check-point inhibition (PMID: 30093446). 30093446
ERBB2 amp Her2-receptor positive breast cancer sensitive TAS0728 Preclinical - Cell line xenograft Actionable In a preclinical study, TAS0728 inhibited Erbb2 downstream signaling and proliferation of ERBB2 (HER2) amplified breast cancer cell lines in culture, and induced tumor regression in cell line xenograft models (PMID: 30787176). 30787176
ERBB2 amp breast cancer sensitive Lapatinib + S63845 Preclinical - Cell culture Actionable In a preclinical study, the combination of S63845 and Tykerb (lapatinib) resulted in potent cytotoxic effects in ERBB2 (HER2)-amplified breast cancer cells in culture compared to the cytostatic effect of Tykerb (lapatinib) alone (PMID: 27760111). 27760111
ERBB2 amp 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 amp 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 amp breast cancer sensitive Torkinib Preclinical - Cell culture Actionable In a preclinical study, ERBB2 (HER2) amplified breast cancer cells treated with Torkinib (PP242) demonstrated some efficacy in culture including reduced phosphorylation of S6 and Akt, apoptosis, and decreased cell growth (PMID: 27197158). 27197158
ERBB2 amp gastric adenocarcinoma no benefit Lapatinib Phase III Actionable In a Phase III clinical trial, the addition of Tykerb (lapatinib) to Xeloda (capecitabine) and Eloxatin (oxaliplatin) combination treatment did not significantly prolong overall survival compared to placebo, but did improve progression-free survival and response rate in gastric adenocarcinoma patients harboring ERBB2 amplification (PMID: 26628478). 26628478
ERBB2 amp 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)-positive breast cancer (NCCN.org). detail...
ERBB2 amp breast cancer sensitive Pertuzumab + Trastuzumab Preclinical - Cell line xenograft Actionable In a preclinical study, breast cancer cell line xenograft models harboring ERBB2 (HER2) amplification were sensitive to the combination of Herceptin (trastuzumab) and Perjeta (pertuzumab), resulting in a delay of brain lesion growth and improved survival (PMID: 28539475). 28539475
ERBB2 amp breast cancer sensitive eFT226 Preclinical - Cell line xenograft Actionable In a preclinical study, eFT226 inhibited cell growth and induced apoptosis in a ERBB2 (HER2)-amplified breast cancer cell line in culture, and induced tumor regression in a cell line xenograft model (Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B133). detail...
ERBB2 amp 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 amp breast cancer sensitive LJM716 + Neratinib Preclinical - Cell line xenograft Actionable In a preclinical study, breast cancer cell line xenograft models harboring ERBB2 (HER2) amplification were sensitive to the combination of LJM716 and Nerlynx (neratinib), resulting in a delay of brain lesion growth and improved survival (PMID: 28539475). 28539475
ERBB2 amp Her2-receptor negative 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 amp stomach cancer sensitive TAS0728 Preclinical - Cell line xenograft Actionable In a preclinical study, TAS0728 inhibited Erbb2 downstream signaling and proliferation of ERBB2 (HER2) amplified gastric cancer cells in culture, and induced tumor regression in cell line xenograft models (PMID: 30787176). 30787176
ERBB2 amp 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 amp colorectal cancer decreased response Lapatinib Preclinical - Pdx Actionable In a preclinical study, treatment with Tykerb (lapatinib) resulted in initial disease stabilization with subsequent progression, in patient-derived colorectal cancer tumorgraft models with ERBB2 (HER2) amplification (PMID: 26296355). 26296355
ERBB2 amp uterine corpus serous adenocarcinoma sensitive SYD985 Preclinical Actionable In a preclinical study, SYD895 induced cell death in ERBB2 (HER2)-amplified primary uterine serous carcinoma (USC) cell lines in culture and inhibited tumor growth and improved survival in ERBB2 (HER2)-amplified USC primary cell line xenografts (PMID: 27256376). 27256376
ERBB2 amp uterine corpus serous adenocarcinoma sensitive Neratinib + Taselisib Preclinical - Cell culture Actionable In a preclinical study, the combination of Taselisib (GDC-0032) and Nerlynx (neratinib) resulted in a synergistic effect, demonstrating greater cell growth inhibitory activity in uterine serous carcinoma cells harboring ERBB2 (HER2) amplification compared to either agent alone (PMID: 26333383). 26333383
ERBB2 amp 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 amp stomach carcinoma no benefit Debio 1347 Preclinical - Cell line xenograft Actionable In a preclinical study, Debio 1347 did not inhibit tumor growth in cell line xenograft models of ERBB2 (HER2) amplified gastric carcinoma (PMID: 26438159). 26438159
ERBB2 amp uterine corpus serous adenocarcinoma sensitive Taselisib Preclinical - Cell culture Actionable In a preclinical study, a uterine serous carcinoma cell line harboring ERBB2 (HER2) amplification demonstrated sensitivity to treatment with Taselisib (GDC-0032) in culture, resulting in inhibition of cell growth (PMID: 26333383). 26333383
ERBB2 amp 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 amp breast cancer sensitive Lapatinib + Torkinib Preclinical - Cell culture Actionable In a preclinical study, the combination therapy of Tykerb (lapatinib) and Torkinib (PP242) in ERBB2 (HER2) amplified breast cancer cells in culture blocked cell growth, inhibited phosphorylation of Akt and S6, and led to greater caspase activity when compared to each agent alone (PMID: 27197158). 27197158
ERBB2 amp breast cancer sensitive Afatinib Preclinical Actionable In a preclinical study, Gilotrif (afatinib) inhibited proliferation of breast cancer cell lines with ERBB2 (HER2) amplification in culture (PMID: 26545934). 26545934
ERBB2 amp gastroesophageal junction adenocarcinoma no benefit Lapatinib Phase III Actionable In a Phase III clinical trial, the addition of Tykerb (lapatinib) to Xeloda (capecitabine) and Eloxatin (oxaliplatin) combination treatment did not significantly prolong overall survival compared to placebo, but did improve progression-free survival and response rate in gastroesophageal junction adenocarcinoma patients harboring ERBB2 amplification (PMID: 26628478). 26628478
ERBB2 amp Advanced Solid Tumor sensitive Afatinib Phase II Actionable In a Phase II trial, Gilotrif (afatinib), demonstrated safety and efficacy in various advanced solid tumor patients with ERBB2 (HER2) amplification (PMID: 23775486). 23775486
ERBB2 amp 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 amp Her2-receptor positive breast cancer predicted - sensitive Poziotinib Phase II Actionable In a Phase II trial, increased copy number (CN) of ERBB2 (HER2) was associated with improved response to Poziotinib (HM781-36B) treatment in patients with Erbb2 (Her2)-positive breast cancer, with a median progression-free survival of 4.86 months in patients with CN over 8 and 2.99 months in patients with CN equal to or less than 8 (HR=0.61, p=0.037) (PMID: 30720867, NCT02418689). 30720867
ERBB2 amp 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 amp Advanced Solid Tumor predicted - sensitive Ado-trastuzumab emtansine Phase II Actionable In a Phase II (MATCH) trial, Kadcyla (trastuzumab emtansine) treatment resulted in partial response in 8.1% (3/37) and stable disease in 43% (16/37) of patients with ERBB2 (HER2) amplified non-breast, non-gastric advanced solid tumors, with a 6-month progression-free survival rate of 24.8% (J Clin Oncol 36, 2018 (suppl; abstr 100); NCT02465060). detail...
ERBB2 amp gastrointestinal system cancer sensitive Dacomitinib Preclinical Actionable In a preclinical study, Vizimpro (dacomitinib) demonstrated significant growth-inhibitory effects in HER2- amplified gastric cancer cells (PMID: 18606718). 18606718
ERBB2 amp esophagus adenocarcinoma no benefit Lapatinib Phase III Actionable In a Phase III clinical trial, the addition of Tykerb (lapatinib) to Xeloda (capecitabine) and Eloxatin (oxaliplatin) combination treatment did not significantly prolong overall survival compared to placebo, but did improve progression-free survival and response rate in esophagus adenocarcinoma patients harboring ERBB2 amplification (PMID: 26628478). 26628478
ERBB2 amp stomach cancer sensitive Lapatinib Preclinical Actionable In preclinical studies, Tykerb (lapatinib) demonstrated antiproliferative activity in HER2-amplified gastric cancer in cell assays and in xenograft models (PMID: 20179222). 20179222
ERBB2 amp 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 amp breast cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, CH5132799 inhibited proliferation of breast cancer cells with ERBB2 (HER2) amplification in culture (PMID: 21558396). 21558396
ERBB2 amp 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). 23801166 detail... detail...
ERBB2 amp 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 amp Her2-receptor positive breast cancer sensitive S63845 + Trastuzumab Preclinical - Pdx & cell culture Actionable In a preclinical study, S63845 and Herceptin (trastuzumab) demonstrated synergy in ERBB2 (HER2)-amplified breast cancer cells in culture and in ERBB2 (HER2)-amplified breast cancer patient-derived xenograft (PDX) models, resulting in enhanced tumor growth inhibition and overall survival compared to either agent alone (PMID: 28768804). 28768804
ERBB2 amp Her2-receptor positive breast cancer sensitive Ado-trastuzumab emtansine Guideline Actionable Kadcyla (ado-trastuzumab emtansine) is included in the guidelines for ERBB2 (HER2)-positive patients with 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). detail... 31236598 30032243
ERBB2 amp 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 23020162 detail... detail...
ERBB2 amp 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 amp 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 amp scrotum Paget's disease predicted - sensitive Ado-trastuzumab emtansine Phase II Actionable In a Phase II (MATCH) trial, Kadcyla (trastuzumab emtansine) treatment resulted in partial response in a patient with ERBB2 (HER2) amplified Paget’s disease of the scrotum (J Clin Oncol 36, 2018 (suppl; abstr 100); NCT02465060). detail...
ERBB2 amp lung non-small cell carcinoma sensitive Afatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Gilotrif (afatinib) inhibited proliferation and induced cell-cycle arrest and apoptosis of non-small cell lung cancer (NSCLC) cell lines with ERBB2 (HER2) amplification in culture, and inhibited tumor growth in ERBB2 (HER2)-amplified NSCLC cell line xenograft models (PMID: 26545934). 26545934
ERBB2 amp 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 amp 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... detail...
ERBB2 amp Her2-receptor positive breast cancer sensitive Capecitabine + Neratinib Guideline Actionable Nerlynx (neratinib) 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 amp 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 amp colorectal cancer resistant Cetuximab Clinical Study - Cohort Actionable In a clinical study, ERBB2 (HER2) amplification was associated with resistance to Erbitux (cetuximab) in colorectal cancer patients (PMID: 21900593). 21900593
ERBB2 amp esophageal cancer sensitive Ibrutinib Preclinical - Cell culture Actionable In a preclinical study, esophageal cancer cells with ERBB2 (HER2) amplification demonstrated sensitivity to Imbruvica (ibrutinib), resulting in decreased survival in culture (PMID: 28830912). 28830912
ERBB2 amp 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 amp lung cancer predicted - sensitive TAS0728 Preclinical - Cell culture Actionable In a preclinical study, TAS0728 inhibited Erbb2 downstream signaling and proliferation of ERBB2 (HER2) amplified lung cancer cells in culture (PMID: 30787176). 30787176
ERBB2 amp FGFR2 wild-type stomach cancer resistant AZD4547 Preclinical Actionable In a preclinical study, gastric cancer cells with wild-type FGFR2 and ERBB2 (HER2) amplification were resistant to treatment with AZD4547 in culture (PMID: 22869148). 22869148
ERBB2 amp PIK3CA C420R breast cancer sensitive CYH33 Preclinical - Cell culture Actionable In a preclinical study, CYH33 inhibited proliferation of breast cancer cell lines harboring PIK3CA C420R and ERBB2 (HER2) amplification in culture (PMID: 30003928). 30003928
ERBB2 amp PIK3CA C420R breast cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, CH5132799 inhibited proliferation of a breast cancer cell line harboring PIK3CA C420R and ERBB2 (HER2) amplification (PMID: 21558396). 21558396
ERBB2 amp PIK3CA N345K breast cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, CH5132799 inhibited proliferation of a breast cancer cell line harboring PIK3CA N345K and ERBB2 (HER2) amplification in culture (PMID: 21558396). 21558396
ERBB2 amp PIK3CA H1047R breast cancer sensitive Gedatolisib Preclinical Actionable In a preclinical study, Gedatolisib (PKI-587) inhibited growth of human breast cancer cells harboring ERBB2 (HER2) amplification and PIK3CA H1047R in culture (PMID: 21325073, PMID: 17314276). 17314276 21325073
ERBB2 amp PIK3CA H1047R ovarian cancer sensitive CH5132799 Preclinical - Cell line xenograft Actionable In a preclinical study, CH5132799 inhibited cell growth in a human ovarian cancer cell line harboring PIK3CA H1047R and ERBB2 (HER2) amplification, and inhibited tumor growth in xenograft models (PMID: 21558396). 21558396
ERBB2 amp PIK3CA H1047R breast cancer sensitive CH5132799 Preclinical - Cell line xenograft Actionable In a preclinical study, CH5132799 inhibited cell growth and Akt phosphorylation, and promoted apoptosis in a human breast cancer cell line harboring PIK3CA H1047R and ERBB2 (HER2) amplification, and inhibited tumor growth in xenograft models (PMID: 21558396). 21558396
ERBB2 amp PIK3CA H1047R breast cancer sensitive CH5132799 + Trastuzumab Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of CH5132799 and Herceptin (trastuzumab) inhibited tumor growth and overcame Herceptin (trastuzumab) insensitivity in xenograft models of a human breast cancer cell line harboring PIK3CA H1047R and ERBB2 (HER2) amplification (PMID: 21558396). 21558396
ERBB2 amp PIK3CA H1047R breast cancer sensitive CYH33 Preclinical - Cell culture Actionable In a preclinical study, CYH33 inhibited proliferation of breast cancer cell lines harboring PIK3CA H1047R and ERBB2 (HER2) amplification in culture (PMID: 30003928). 30003928
ERBB2 amp PIK3CA K111N breast cancer sensitive CH5132799 Preclinical - Cell line xenograft Actionable In a preclinical study, CH5132799 inhibited cell growth and Akt phosphorylation, and promoted apoptosis in a human breast cancer cell line harboring PIK3CA K111N and ERBB2 (HER2) amplification, and inhibited tumor growth in xenograft models (PMID: 21558396). 21558396
ERBB2 amp PIK3CA K111N breast cancer predicted - sensitive CYH33 Preclinical - Cell culture Actionable In a preclinical study, CYH33 inhibited proliferation of a breast cancer cell line harboring PIK3CA K111N and ERBB2 (HER2) amplification in culture (PMID: 30003928). 30003928
ERBB2 amp PIK3CA E545K breast cancer sensitive CH5132799 Preclinical Actionable In a preclinical study, CH5132799 inhibited proliferation of a breast cancer cell line harboring PIK3CA E545K and ERBB2 (HER2) amplification in culture (PMID: 21558396). 21558396
ERBB2 amp PIK3CA E545K breast cancer predicted - sensitive CYH33 Preclinical - Cell culture Actionable In a preclinical study, CYH33 inhibited proliferation of a breast cancer cell line harboring PIK3CA E545K and ERBB2 (HER2) amplification in culture (PMID: 30003928). 30003928
ERBB2 amp PIK3CA E545K breast cancer sensitive Buparlisib Preclinical - Cell line xenograft Actionable In a preclinical study, a breast cancer cell line xenograft model co-harboring ERBB2 (HER2) amplification and PIK3CA E545K demonstrated tumor regression within the mammary fat pad when treated with Buparlisib (BKM120) (PMID: 28539475). 28539475
ERBB2 amp PIK3CA E545K PIK3CA K567R Her2-receptor positive breast cancer sensitive Gedatolisib Preclinical - Cell line xenograft Actionable In a preclinical study, Gedatolisib (PKI-587) inhibited PI3K signaling, cell growth and induced apoptosis in human breast cancer cells harboring ERBB2 (HER2) amplification, PIK3CA E545K, and PIK3CA K567R in culture and in cell line xenografts (PMID: 21325073, PMID: 17314276). 17314276 21325073
ERBB2 amp PIK3CA mut breast cancer sensitive CUDC-907 Preclinical Actionable In a preclinical study, CUDC-907 inhibited downstream signaling and growth of PIK3CA-mutant breast cancer cells with ERBB2 amplification in culture (PMID: 22693356). 22693356
ERBB2 amp PIK3CA mut uterine corpus serous adenocarcinoma sensitive Neratinib + Taselisib Preclinical - Cell line xenograft Actionable In a preclinical study, the combination of Nerlynx (neratinib) and Taselisib (GDC-0032), compared to either agent alone, resulted in greater inhibition of cell cycle activity in a uterine serous carcinoma cell line harboring ERBB2 (HER2) amplification and a PIK3CA mutation in culture, and in xenograft models, showed increased tumor growth inhibition and tumor regression (PMID: 26333383). 26333383
ERBB2 amp PIK3CA mut Her2-receptor positive breast cancer sensitive Ipatasertib Preclinical - Cell line xenograft Actionable In a preclinical study, ERBB2 (HER2)-receptor positive breast cancer cell line xenograft models harboring amplification of ERBB2 (HER2) and a PIK3CA mutation demonstrated sensitivity to treatment with Ipatasertib (GDC-0068), resulting in inhibition of tumor growth (PMID: 24141624). 24141624
ERBB2 amp PIK3CA mut Her2-receptor positive breast cancer sensitive Copanlisib Preclinical - Cell line xenograft Actionable In a preclinical study, Aliqopa (copanlisib) promoted tumor regression in xenograft models of a human ERBB2 (HER2)-amplified breast cancer cell line harboring a PIK3CA activating mutation (PMID: 24170767). 24170767
ERBB2 T798M ERBB2 amp breast cancer resistant Trastuzumab Preclinical - Cell line xenograft Actionable In a preclinical study, a human ERBB2-amplified breast cancer cell line expressing ERBB2 (HER2) T798M was resistant to Herceptin (trastuzumab) in culture and in xenograft models (PMID: 23948973). 23948973
ERBB2 L866M ERBB2 amp colorectal cancer resistant Cetuximab Preclinical Actionable In a preclinical study, xenograft models of patient derived colorectal cancer cells harboring ERBB2 (HER2) L866M and ERBB2 (HER2) amplification were resistant to Erbitux (cetuximab) (PMID: 26243863). 26243863
ERBB2 L866M ERBB2 amp colorectal cancer sensitive Neratinib Preclinical Actionable In a preclinical study, Nerlynx (neratinib) treatment resulted in stable tumor size in xenograft models of patient derived colorectal cancer cells harboring ERBB2 (HER2) L866M and ERBB2 (HER2) amplification (PMID: 26243863). 26243863
ERBB2 L866M ERBB2 amp colorectal cancer sensitive Neratinib + Trastuzumab Preclinical Actionable In a preclinical study, Herceptin (trastuzumab) and Nerlynx (neratinib) combination treatment resulted in sustained tumor regression in xenograft models of patient derived colorectal cancer cells harboring ERBB2 (HER2) L866M and ERBB2 (HER2) amplification (PMID: 26243863). 26243863
ERBB2 L866M ERBB2 amp colorectal cancer resistant Trastuzumab Preclinical Actionable In a preclinical study, Herceptin (trastuzumab) had no effect on tumor growth in xenograft models of patient derived colorectal cancer cells harboring ERBB2 (HER2) L866M and ERBB2 (HER2) amplification (PMID: 26243863). 26243863
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 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 PIK3CA wild-type uterine corpus serous adenocarcinoma sensitive Neratinib Preclinical - Cell line xenograft Actionable In a preclinical study, Nerlynx (neratinib) delayed cell cycle activity during treatment of a uterine serous carcinoma cell line harboring PIK3CA wild-type and ERBB2 (HER2) amplification in culture, and inhibited tumor growth in xenograft models (PMID: 26333383). 26333383
ERBB2 amp PIK3CA wild-type uterine corpus serous adenocarcinoma sensitive Neratinib + Taselisib Preclinical - Cell culture Actionable In a preclinical study, the combination of Taselisib (GDC-0032) and Nerlynx (neratinib) delayed cell cycle activity in a uterine serous carcinoma cell line harboring PIK3CA wild-type and ERBB2 (HER2) amplification in culture (PMID: 26333383). 26333383
ERBB2 amp PIK3CA wild-type Her2-receptor positive breast cancer predicted - sensitive Poziotinib Phase II Actionable In a Phase II trial, the presence of high ERBB2 (HER2) copy number and wild-type PIK3CA correlated with improved progression-free survival (HR=0.45, p=0.024) in patients with metastatic Erbb2 (Her2)-positive (amplification or overexpression) breast cancer treated with Poziotinib (HM781-36B) (PMID: 30720867, NCT02418689). 30720867
ERBB2 amp PIK3CA wild-type uterine corpus serous adenocarcinoma sensitive Taselisib Preclinical - Cell line xenograft Actionable In a preclinical study, Taselisib (GDC-0032) did not result in delay of cell cycle activity during treatment of a uterine serous carcinoma cell line harboring PIK3CA wild-type and ERBB2 (HER2) amplification in culture, however, did result in tumor growth inhibition in xenograft models (PMID: 26333383). 26333383
ARID1A loss ERBB2 amp breast cancer sensitive MK2206 + Trastuzumab Preclinical - Cell culture Actionable In a preclinical study, a breast cancer cell line with ARID1A loss and harboring ERBB2 (HER2) amplification demonstrated restored sensitivity to Herceptin (trastuzumab) when additionally treated with MK2206 in culture (PMID: 27172896). 27172896
ERBB2 amp FGFR2 amp esophagus adenocarcinoma sensitive AZD4547 + Lapatinib Preclinical - Cell culture Actionable In a preclinical study, the combination of AZD-4547 and Tykerb (lapatinib) worked synergistically to inhibit growth of an esophageal adenocarcinoma cell line with ERBB2 (HER2) and FGFR2 amplification in culture (PMID: 27595477). 27595477
ERBB2 L755S ERBB2 amp Her2-receptor positive breast cancer decreased response Trastuzumab Preclinical - Cell culture Actionable In a preclinical study, breast cancer cell lines with ERBB2 (HER2) amplification and expressing ERBB2 L755S demonstrated decreased inhibition proliferation compared to cells expressing wild-type ERBB2 (HER2) following treatment with Herceptin (trastuzumab) (PMID: 30301790). 30301790
ERBB2 L755S ERBB2 amp Her2-receptor positive breast cancer resistant Lapatinib Preclinical - Cell line xenograft Actionable In a preclinical study, ERBB2 (HER2) L755S was associated with reactivation of ERBB2 (HER2) signaling and acquired resistance to Tykerb (lapatinib) in ESR1-positive/ERBB2 (HER2)-positive breast cancer cell lines with ERBB2 amplification in culture and in xenograft models (PMID: 28487443). 28487443
ERBB2 L755S ERBB2 amp Her2-receptor positive breast cancer resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, breast cancer cell lines with ERBB2 (HER2) amplification and expressing ERBB2 L755S demonstrated decreased inhibition of ERBB2 (HER2) signaling and proliferation compared to cells expressing wild-type ERBB2 (HER2) following treatment with Tykerb (lapatinib) (PMID: 30301790). 30301790
ERBB2 L755S ERBB2 amp Her2-receptor positive breast cancer sensitive Afatinib Preclinical - Cell line xenograft Actionable In a preclinical study, Gilotrif (afatinib) inhibited growth of ESR1-positive/ERBB2 (HER2)-positive breast cancer cell lines with ERBB2 amplification and harboring ERBB2 L755S in culture, and inhibited tumor growth in xenograft models (PMID: 28487443). 28487443
ERBB2 L755S ERBB2 amp Her2-receptor positive breast cancer resistant Pertuzumab + Trastuzumab Preclinical - Cell culture Actionable In a preclinical study, expression of ERBB2 (HER2) L755S conferred resistance to Perjeta (pertuzumab) plus Herceptin (trastuzumab) combination therapy in ESR1-positive/ERBB2 (HER2)-positive breast cancer cells with ERBB2 amplification in culture (PMID: 28487443). 28487443
ERBB2 L755S ERBB2 amp Her2-receptor positive breast cancer sensitive Neratinib Preclinical - Cell culture Actionable In a preclinical study, Nerlynx (neratinib) inhibited growth of ESR1-positive/ERBB2 (HER2)-positive breast cancer cell lines with ERBB2 amplification and harboring ERBB2 L755S in culture (PMID: 28487443). 28487443
ERBB2 L755S ERBB2 amp Her2-receptor positive breast cancer sensitive Neratinib Case Reports/Case Series Actionable In a clinical study, Nerlynx (neratinib) treatment resulted in partial response in 2 of 6 and disease stabilization in 4 of 6 breast cancer patients with ERBB2 (HER2) amplification and an ERBB2 (HER2) mutation, including stable disease in a patient harboring ERBB2 (HER2) L755S, and breast cancer cell lines with ERBB2 (HER2) amplification and expressing ERBB2 (HER2) L755S demonstrated sensitivity to Nerlynx (neratinib) in culture (PMID: 30301790). 30301790
ERBB2 L755S ERBB2 amp Her2-receptor positive breast cancer decreased response Ado-trastuzumab emtansine Preclinical - Cell culture Actionable In a preclinical study, expression of ERBB2 (HER2) L755S resulted in decreased sensitivity to treatment with Kadcyla (trastuzumab emtansine) in ESR1-positive/ERBB2 (HER2)-positive breast cancer cells with ERBB2 amplification in culture (PMID: 28487443). 28487443
ERBB2 L755S ERBB2 amp Her2-receptor positive breast cancer resistant Lapatinib + Trastuzumab Preclinical - Cell culture Actionable In a preclinical study, breast cancer cell lines with ERBB2 (HER2) amplification and expressing ERBB2 L755S demonstrated decreased inhibition proliferation compared to cells expressing wild-type ERBB2 (HER2) following treatment with Herceptin (trastuzumab) and Tykerb (lapatinib) (PMID: 30301790). 30301790
ERBB2 L755S ERBB2 amp Her2-receptor positive breast cancer resistant Lapatinib + Trastuzumab Preclinical - Cell culture Actionable In a preclinical study, expression of ERBB2 (HER2) L755S conferred resistance to Tykerb (lapatinib) plus Herceptin (trastuzumab) combination therapy in ESR1-positive/ERBB2 (HER2)-positive breast cancer cells with ERBB2 amplification in culture (PMID: 28487443). 28487443
ERBB2 amp SRC E527K gastroesophageal junction adenocarcinoma resistant Lapatinib Preclinical - Cell culture Actionable In a preclinical study, an ERBB2 (HER2)-amplified gastroesophageal cancer cell line initially sensitive to treatment with Tykerb (lapatinib) in culture developed resistance and was subsequently found to have acquired a secondary drug resistant mutation, SRC E527K (PMID: 25350844). 25350844
ERBB2 amp SRC E527K gastroesophageal junction adenocarcinoma sensitive Lapatinib + Saracatinib Preclinical - Cell culture Actionable In a preclinical study, the combination of Tykerb (lapatinib) and Saracatinib (AZD0530) inhibited growth of ERBB2 (HER2)-amplified gastroesophageal adenocarcinoma cells harboring SRC E527K in culture (PMID: 25350844). 25350844
ROS1 fusion ERBB2 amp NOTCH1 amp SRC amp STK11 amp lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor presumed resistance alterations, including amplification of SRC, ERBB2 (HER2), STK11, and NOTCH1 (PMID: 29636358). 29636358
ROS1 fusion ERBB2 amp FGFR3 amp RET amp lung non-small cell carcinoma predicted - resistant Crizotinib Case Reports/Case Series Actionable In a clinical study, a non-small cell lung carcinoma patient harboring a ROS1 fusion treated with Xalkori (crizotinib) responded, but eventually progressed, and was subsequently found to harbor presumed resistance alterations, including amplification of ERBB2 (HER2), FGFR3, and RET (PMID: 29636358). 29636358
ERBB2 S310F ERBB2 amp lung adenocarcinoma predicted - sensitive Ado-trastuzumab emtansine Case Reports/Case Series Actionable In a Phase II trial, treatment with Kadcyla (trastuzumab emtansine) resulted in best overall responses of partial response in 44% (8/18) and stable disease in 39% (7/18), and median progression-free survival of 5 months in patients with lung adenocarcinoma harboring ERBB2 (HER2) activating mutations; a patient harboring ERBB2 (HER2) S310F and ERBB2 (HER2) amplification had a partial response (PMID: 29989854; NCT02675829). 29989854
ERBB2 Y772_A775dup ERBB2 amp Her2-receptor positive breast cancer predicted - sensitive Neratinib Case Reports/Case Series Actionable In a clinical study, Nerlynx (neratinib) treatment resulted in partial response in 2 of 6 and disease stabilization in 4 of 6 breast cancer patients with ERBB2 (HER2) amplification and an ERBB2 (HER2) mutation, including stable disease in a patient harboring ERBB2 (HER2) Y772_A775dup (PMID: 30301790). 30301790
ERBB2 D769Y ERBB2 amp Her2-receptor positive breast cancer sensitive Neratinib Case Reports/Case Series Actionable In a clinical study, Nerlynx (neratinib) treatment resulted in partial response in 2 of 6 and disease stabilization in 4 of 6 breast cancer patients with ERBB2 (HER2) amplification and an ERBB2 (HER2) mutation, including stable disease in a patient harboring ERBB2 (HER2) D769Y, and Nerlynx (neratinib) inhibited tumor growth in a breast cancer patient-derived xenograft (PDX) model with ERBB2 (HER2) amplification and ERBB2 (HER2) D769Y (PMID: 30301790). 30301790
ERBB2 D769Y ERBB2 amp Her2-receptor positive breast cancer resistant Trastuzumab Preclinical - Pdx Actionable In a preclinical study, a breast cancer patient-derived xenograft (PDX) model with ERBB2 (HER2) amplification and ERBB2 D769Y was refractory to treatment with Herceptin (trastuzumab) (PMID: 30301790). 30301790
ERBB2 D769Y ERBB2 amp Her2-receptor positive breast cancer resistant Lapatinib Preclinical - Pdx Actionable In a preclinical study, a breast cancer patient-derived xenograft (PDX) model with ERBB2 (HER2) amplification and ERBB2 D769Y was refractory to treatment with Tykerb (lapatinib) (PMID: 30301790). 30301790
ERBB2 V777L ERBB2 amp Her2-receptor positive breast cancer predicted - sensitive Neratinib Case Reports/Case Series Actionable In a clinical study, Nerlynx (neratinib) treatment resulted in partial response in 2 of 6 and disease stabilization in 4 of 6 breast cancer patients with ERBB2 (HER2) amplification and an ERBB2 (HER2) mutation, including partial response in a patient harboring ERBB2 (HER2) V777L (PMID: 30301790). 30301790
ERBB2 L313I ERBB2 amp Her2-receptor positive breast cancer predicted - sensitive Neratinib Case Reports/Case Series Actionable In a clinical study, Nerlynx (neratinib) treatment resulted in partial response in 2 of 6 and disease stabilization in 4 of 6 breast cancer patients with ERBB2 (HER2) amplification and an ERBB2 (HER2) mutation, including partial response in a patient harboring ERBB2 (HER2) L313I (PMID: 30301790). 30301790
ERBB2 R456C ERBB2 amp Her2-receptor positive breast cancer predicted - sensitive Neratinib Case Reports/Case Series Actionable In a clinical study, Nerlynx (neratinib) treatment resulted in partial response in 2 of 6 and disease stabilization in 4 of 6 breast cancer patients with ERBB2 (HER2) amplification and an ERBB2 (HER2) mutation, including stable disease in a patient harboring ERBB2 (HER2) R456C (PMID: 30301790). 30301790
ERBB2 amp 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 amp 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 amp 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
ERBB2 amp 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
BRAF wild-type ERBB2 amp NRAS wild-type colon cancer sensitive Pertuzumab + Trastuzumab Guideline Actionable Herceptin (trastuzumab) in combination with Perjeta (pertuzumab) is included in guidelines as second-line therapy for advanced or metastatic colon cancer patients with ERBB2 amplification and NRAS, BRAF wild-type (NCCN.org). detail...
BRAF wild-type ERBB2 amp NRAS wild-type colon cancer sensitive Lapatinib + Trastuzumab Guideline Actionable Herceptin (trastuzumab) in combination with Tykerb (lapatinib) is included in guidelines as second-line therapy for advanced or metastatic colon cancer patients with ERBB2 amplification and NRAS, BBRAF wild-type (NCCN.org). detail...
BRAF wild-type ERBB2 amp NRAS wild-type rectum cancer sensitive Lapatinib + Trastuzumab Guideline Actionable Herceptin (trastuzumab) in combination with Tykerb (lapatinib) is included in guidelines as second-line therapy for advanced or metastatic rectum cancer patients with ERBB2 amplification and wild-type NRAS and BRAF (NCCN.org). detail...
BRAF wild-type ERBB2 amp NRAS wild-type rectum cancer sensitive Pertuzumab + Trastuzumab Guideline Actionable Herceptin (trastuzumab) in combination with Perjeta (pertuzumab) is included in guidelines as second-line therapy for advanced or metastatic rectum cancer patients with ERBB2 amplification and wild-type NRAS and BRAF (NCCN.org). detail...