Reference Detail

Contact

Missing content? – Request curation!

Request curation for specific Genes, variants, or PubMed publications.

Have questions, comments or suggestions? - Let us know!

Email us at : ckbsupport@jax.org

Ref Type Journal Article
PMID (30596880)
Authors Wang Y, Jiang T, Qin Z, Jiang J, Wang Q, Yang S, Rivard C, Gao G, Ng TL, Tu MM, Yu H, Ji H, Zhou C, Ren S, Zhang J, Bunn P, Doebele RC, Camidge DR, Hirsch FR
Title HER2 exon 20 insertions in non-small-cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib.
Journal Annals of oncology : official journal of the European Society for Medical Oncology
Vol 30
Issue 3
Date 2019 03 01
URL
Abstract Text Effective targeted therapy for non-small-cell lung cancer (NSCLC) patients with human epidermal growth factor receptor 2 (HER2) mutations remains an unmet need. This study investigated the antitumor effect of an irreversible pan-HER receptor tyrosine kinase inhibitor, pyrotinib.Using patient-derived organoids and xenografts established from an HER2-A775_G776YVMA-inserted advanced lung adenocarcinoma patient sample, we investigated the antitumor activity of pyrotinib. Preliminary safety and efficacy of pyrotinib in 15 HER2-mutant NSCLC patients in a phase II clinical trial are also presented.Pyrotinib showed significant growth inhibition of organoids relative to afatinib in vitro (P = 0.0038). In the PDX model, pyrotinib showed a superior antitumor effect than afatinib (P = 0.0471) and T-DM1 (P = 0.0138). Mice treated with pyrotinib displayed significant tumor burden reduction (mean tumor volume, -52.2%). In contrast, afatinib (25.4%) and T-DM1 (10.9%) showed no obvious reduction. Moreover, pyrotinib showed a robust ability to inhibit pHER2, pERK and pAkt. In the phase II cohort of 15 patients with HER2-mutant NSCLC, pyrotinib 400 mg resulted in a objective response rate of 53.3% and a median progression-free survival of 6.4 months.Pyrotinib showed activity against NSCLC with HER2 exon 20 mutations in both patient-derived organoids and a PDX model. In the clinical trial, pyrotinib showed promising efficacy.NCT02535507.

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"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Pyrotinib SHR-1258|SHR1258 EGFR Inhibitor (Pan) 46 HER2 Inhibitor 23 Pyrotinib is an irreversible dual inhibitor of EGFR and ERBB2 (HER2), which potentially leads to decreased growth of EGFR and/or HER2-positive tumor cells (PMID: 28115222, PMID: 30596880).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ERBB2 G776delinsVC lung non-small cell carcinoma predicted - sensitive Pyrotinib Case Reports/Case Series Actionable In a Phase II trial, a patient with non-small cell lung cancer harboring ERBB2 G776delinsVC demonstrated a partial response and an ongoing progression-free survival when treated with Pyrotinib (PMID: 30596880; NCT02535507). 30596880
ERBB2 L755P lung non-small cell carcinoma predicted - sensitive Pyrotinib Case Reports/Case Series Actionable In a Phase II trial, a patient with non-small cell lung cancer harboring ERBB2 L755P demonstrated a partial response when treated with Pyrotinib (PMID: 30596880; NCT02535507). 30596880
ERBB2 P780_Y781insGSP lung non-small cell carcinoma predicted - sensitive Pyrotinib Case Reports/Case Series Actionable In a Phase II trial, a patient with non-small cell lung cancer harboring ERBB2 P780_Y781insGSP demonstrated stable disease and progression-free survival for more than one year when treated with Pyrotinib (PMID: 30596880; NCT02535507). 30596880
ERBB2 A775_G776insYVMA lung non-small cell carcinoma sensitive Pyrotinib Case Reports/Case Series Actionable In a Phase II trial, ten patients with non-small cell lung cancer harboring ERBB2 A775_G776insYVMA demonstrated an objective response rate of 50% (5/10) and a progression-free survival of 4.1 months when treated with Pyrotinib, and preclinical analysis showed Pyrotinib treatment led to reduced cell viability in patient-derived organoids and tumor growth inhibition and regression in patient derived xenograft (PDX) models (PMID: 30596880; NCT02535507). 30596880
ERBB2 exon20 lung non-small cell carcinoma predicted - sensitive Pyrotinib Phase II Actionable In a Phase II trial, non-small cell lung cancer patients harboring an ERBB2 exon 20 mutation demonstrated an objective response rate of 53.3% (8/15) and a median progression-free survival of 6.4 months when treated with Pyrotinib (PMID: 30596880; NCT02535507). 30596880
ERBB2 A775_G776insYVMA lung non-small cell carcinoma sensitive Ado-trastuzumab emtansine Preclinical - Pdx Actionable In a preclinical study, treatment with Kadcyla (ado-trastuzumab emtansine) resulted in tumor growth inhibition and tumor regression of patient derived xenograft (PDX) models harboring ERBB2 A775_G776insYVMA, but to a lesser degree than treatment with Pyrotinib (PMID: 30596880; NCT02535507). 30596880
ERBB2 G776delinsIC lung non-small cell carcinoma no benefit Pyrotinib Case Reports/Case Series Actionable In a Phase II trial, a patient with non-small cell lung cancer harboring ERBB2 G776delinsIC did not respond to treatment with Pyrotinib and developed progressive disease (PMID: 30596880; NCT02535507). 30596880
ERBB2 G776C lung non-small cell carcinoma predicted - sensitive Pyrotinib Case Reports/Case Series Actionable In a Phase II trial, a patient with non-small cell lung cancer harboring ERBB2 G776C demonstrated a partial response when treated with Pyrotinib (PMID: 30596880; NCT02535507). 30596880
ERBB2 A775_G776insYVMA lung non-small cell carcinoma sensitive Afatinib Preclinical - Pdx & cell culture Actionable In a preclinical study, treatment with Gilotrif (afatinib) resulted in decreased cell viability of patient-derived non-small cell lung cancer organoids harboring ERBB2 A775_G776insYVMA and tumor growth inhibition and tumor regression in patient derived xenograft (PDX) models, but to a lesser degree than treatment with Pyrotinib (PMID: 30596880; NCT02535507). 30596880