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Association details:
| Biomarker: | HER-2 exon 20 insertion |
|---|---|
| Cancer: | HER2 Positive Breast Cancer |
| Drug: | Nerlynx (neratinib) (EGFR inhibitor, HER2 inhibitor, HER4 inhibitor) + Kadcyla (ado-trastuzumab emtansine) (Microtubule inhibitor, HER2-targeted antibody-drug conjugate) |
| Direction: | Sensitive |
Evidence:
Source:
Title:
Irreversible inhibition of HER2 activating mutations with neratinib enhances the pre-clinical efficacy of trastuzumab emtansine and trastuzumab deruxtecan
Published date:
11/17/2020
Excerpt:
WHIM51 has HER2 exon 20 insertion mutation at amino acid 776 (ERBB2 A775_G776insYVMA) and WHIM64 has a HER2 L869R missense mutation....We have tested both the combinations of neratinib + T-DXd and neratinib + T-DM1 in vivo in both HER2 mutant PDX’s and observed statistically significant tumor regression with the neratinib + ADC combinations as compared to either T-DXd or T-DM1 on its own....Neratinib increases the endocytosis of trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd), thereby increasing tumor cell kill and causing greater tumor regression in HER2 mutated MBC.
