Mechanism

NERLYNX provides comprehensive, irreversible intracellular pan-HER signaling inhibition17-20,*

Sustained inhibition of signaling leads to increased tumor cell death

EGFR: epidermal growth factor receptor; HER: human epidermal growth factor receptor; MAPK: mitogen-activated protein kinase

*As observed in preclinical models.17


NERLYNX is a small molecule that induces tumor cell death3,17,21

The first and only HER2-directed small molecule approved in early-stage breast cancer

Crossing the blood-brain barrier:

  • In preclinical studies using an in vitro model, neratinib, a low molecular-weight drug, demonstrated the ability to cross the blood-brain barrier3,21-23
  • In preclinical studies, neratinib inhibited key transporters associated with drug resistance in the brain21-23

NERLYNX may inhibit HER2-ER crosstalk24

Adding NERLYNX to your antiestrogen regimen may inhibit HER2 and ER crosstalk, leading to more comprehensive anti-tumor activity24

A HER2 escape mechanism

Crosstalk between ER and HER2 pathways may cause treatments that target only on pathway to upregulate the other nontargeted pathway24,25

Comprehensive anti-tumor activity

Adding NERLYNX to endocrine therapy may inhibit this key mechanism of resistance24

ER: estrogen receptor; HER: human epidermal growth factor receptor


Despite monoclonal antibody inhibition, resistance mechanisms allow tumors to proliferate24,26

In early-stage HER2+ breast cancer

EGFR: epidermal growth factor receptor; HER: human epidermal growth factor receptor

Resistance escape mechanisms can be grouped into 4 categories24,26,27

Truncation and masking

Truncation and masking of the extracellular domain prevents binding of the monoclonal antibody to the HER2 receptor26

Resistance escape mechanisms can be grouped into 4 categories24,26,27

Lack of immune response

Despite antibody binding and weakened signaling, the immune system is unable to engage and kill the tumor cell24,26-28

Crosstalk

Increased HER signaling drives down ER-dependent gene expression; inhibiting HER signaling results in a compensatory increase in ER-dependent gene expression24,25,27,29,30

Upregulation

Upregulation of HER2 downstream signaling pathways such as PI3K/AKT after loss of PTEN tumor suppression gene functioning can diminish HER2-targeted inhibition26

AKT: protein kinase B; ER: estrogen receptor; HER: human epidermal growth factor receptor; PI3K: phosphoinositide 3-kinase; PTEN: phosphatase and tensin homolog

Addressing resistance mechanisms with a pan-HER, irreversible, intracellular blockade of pathways may help prevent tumor escape.17-19

Select IMPORTANT SAFETY INFORMATION

Diarrhea: Aggressively manage diarrhea occurring despite recommended prophylaxis with additional antidiarrheals, fluids, and electrolytes as clinically indicated. Withhold NERLYNX in patients experiencing severe and/or persistent diarrhea. Permanently discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade ≥ 2 diarrhea that occurs after maximal dose reduction.

Please see additional IMPORTANT SAFETY INFORMATION below.

See NERLYNX efficacy data

IMPORTANT SAFETY INFORMATION

NERLYNX® (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

ADVERSE REACTIONS: The most common adverse reactions (>5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight decreased and urinary tract infection.

To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) and www.NERLYNX.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS:

USE IN SPECIFIC POPULATIONS:

For Full Prescribing Information, please click here.