Mechanism

NERLYNX provides comprehensive, irreversible intracellular pan-HER signaling inhibition9-11,*

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.9

HER-ER crosstalk is an important consideration in patients with HER2+, ER+ disease12-15

HER and ER crosstalk

Crosstalk between aberrant HER signaling and the estrogen receptor (ER) pathway downregulates ER-dependent gene expression12-14

Inhibiting HER signaling results in a compensatory increase in ER-dependent gene expression12,15

Combining NERLYNX and antiestrogens inhibits the HER and ER crosstalk, leading to more comprehensive antitumor activity14

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


Resistance mechanisms allow HER2+ breast cancer tumor cells to proliferate, despite monoclonal antibody inhibition14,16

In early-stage HER2+ breast cancer

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

Resistance mechanisms can be grouped into 4 categories14-18

Truncation and masking

Truncation and masking of the extracellular domain prevents binding of the monoclonal antibody to the HER2 receptor16

Lack of immune response

Despite antibody binding, signaling is weak and the immune system is unable to engage and kill the tumor cell14,16-18

Crosstalk

Increased HER signaling drives down ER-dependent gene expression; inhibiting HER signaling results in a compensatory increase in ER-dependent gene expression12-15,17

Upregulation

Upregulation of HER2 downstream signaling pathways such as PI3K/AKT after loss of PTEN tumor suppression gene functioning can diminish HER2-targeted inhibition16

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

Inhibiting resistance mechanisms with a pan-HER, irreversible, intracellular blockade of pathways may help prevent tumor escape.9-11

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.