Molecular Profile Detail

Profile Name ERBB2 S310F
Gene Variant Detail

ERBB2 S310F (gain of function)

Relevant Treatment Approaches HER inhibitor (Pan) HER2 Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
ERBB2 S310F ERBB2 V842I breast cancer predicted - sensitive HER2 Inhibitor Neratinib Phase II Actionable In a Phase II trial, Nerlynx (neratinib) demonstrated activity in metastatic breast cancer patients harboring ERBB2 (HER2) mutations, resulting in a clinical benefit rate of 31% (5/16), with 1 complete response, 1 partial response, and 3 patients achieving stable disease for 24 weeks or more, which included a patient harboring ERBB2 (HER2) S310F and V842I (PMID: 28679771). 28679771
ERBB2 D277G ERBB2 S310F urinary bladder cancer predicted - resistant HER2 Inhibitor Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.7 months in a patient with bladder cancer harboring both ERBB2 (HER2) D277G and S310F (PMID: 29420467; NCT01953926). 29420467
ERBB2 D277H ERBB2 S310F urinary bladder cancer sensitive HER inhibitor (Pan) Afatinib Preclinical Actionable In a preclinical study, Gilotrif (afatinib) inhibited foci formation of bladder cancer cells over expressing both ERBB2 (HER2) D277H and S310F in culture (PMID: 24971884). 24971884
ERBB2 D277H ERBB2 S310F urinary bladder cancer decreased response Selumetinib Preclinical Actionable In a preclinical study, bladder cancer cells over expressing both ERBB2 (HER2) D277H and S310F demonstrated reduced sensitivity to Selumetinib (AZD6244) in culture (PMID: 24971884). 24971884
ERBB2 D277H ERBB2 S310F urinary bladder cancer sensitive Lapatinib Preclinical Actionable In a preclinical study, Tykerb (lapatinib) inhibited foci formation of bladder cancer cells over expressing both ERBB2 (HER2) D277H and S310F in culture (PMID: 24971884). 24971884
ERBB2 amp ERBB2 S310F 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 S310F ERBB2 G660D ampulla of Vater carcinoma predicted - sensitive HER inhibitor (Pan) Afatinib Case Reports/Case Series Actionable In a clinical case study, Gilotrif (afatinib) treatment resulted in stable disease with slight lymph node metastasis reduction in a patient with ampulla of Vater carcinoma harboring ERBB2 S310F and G660D, but the disease eventually progressed after 4 months (PMID: 29146616). 29146616
Clinical Trial Phase Therapies Title Recruitment Status
NCT02675829 Phase II Ado-trastuzumab emtansine Trial of Ado-Trastuzumab Emtansine for Patients With HER2 Amplified or Mutant Cancers Active, not recruiting
NCT02673398 Phase II Neratinib Neratinib in Treating Older Patients With Locally Advanced or Metastatic HER2-Positive Breast Cancer Active, not recruiting