Mechanism of action

NERLYNX provides comprehensive, irreversible intracellular pan-HER signaling inhibition10-12,*

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 seen in preclinical models. 10

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

HER and ER crosstalk

Crosstalk between aberrant HER signaling and the estrogen receptor (ER) pathway drives down ER-dependent gene expression13-15

Inhibiting HER signaling results in a compensatory increase in ER-dependent gene expression13,16

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

Combining NERLYNX and antiestrogens inhibits the HER and ER crosstalk, leading to more comprehensive antitumor activity15

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

Select IMPORTANT SAFETY INFORMATION

Drug interactions: 1. Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors (PPI) and H2-receptor antagonists. Separate NERLYNX by 3 hours after antacid dosing. 2. Strong or moderate CYP3A4 inhibitors: Avoid concomitant use. 3. Strong or moderate CYP3A4 inducers: Avoid concomitant use. 4. P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of narrow therapeutic agents that are P-gp substrates when used concomitantly with NERLYNX.

Please see additional IMPORTANT SAFETY INFORMATION below.

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, epistaxis, 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.