A HER2 escape mechanism
When ER is inhibited with endocrine therapy, crosstalk may cause upregulation of the HER2 pathway2
Dual Blockade
Simultaneous HER2 and ER blockade may inhibit this key mechanism of resistance2,†
Indications: Nerlynx® (neratinib) tablets, for oral use, is a kinase inhibitor indicated:
- As a single agent, for the extended adjuvant treatment of adult patients with early-stage HER2-positive breast cancer, to follow adjuvant trastuzumab-based therapy.
Nerlynx is the first and only HER2-directed small molecule approved in both early-stage and metastatic HER2+ breast cancer1
Nerlynx is a small molecule that demonstrates irreversible intracellular pan-HER signaling inhibition2
PAN-HER RECEPTOR TARGETING WITH NERATINIB
- Irreversibly inhibits HER1 (EGFR), HER2, and HER4 signaling2
- Also inhibits active HER3 heterodimer signaling by interfering with downstream signaling2
ANTI-TUMOR ACTIVITY OF NERATINIB
- Intracellular binding to the receptor tyrosine kinase signaling domain leads to sustained inhibition of signaling, inducing cell cycle arrest and apoptosis2
- Inhibition of downstream signaling reduces tumor cell growth and proliferation and induces tumor cell death in vitro2
NERATINIB AND THE BLOOD-BRAIN BARRIER
- Neratinib passed through a cellular model of the blood-brain barrier, reducing the growth of HER2+ breast cancer cells2,*,†
- In vitro model consisted of brain and endothelial cells which were observed over 72 hours.2
- The impact of neratinib on the blood-brain barrier has not been shown in clinical studies. Any impact is hypothesized, and no potential efficacy or safety implications can be drawn.2
- EGFR: epidermal growth factor receptor; MAPK: mitogen-activated protein kinase; PI3K: phosphatidylinositol 3-kinase; RAS: rat sarcoma virus.
Nerlynx impact on HER2-ER crosstalk2,*
HER2 blockade helps inhibit her2-er crosstalk in her2+ er+ disease2,†
- As seen in preclinical models.2
- The impact of neratinib on the simultaneous HER2 and ER blockade has not been shown in clinical studies. Any impact is hypothesized, and no potential efficacy or safety implications can be drawn.2
- ER: estrogen receptor.
References:
- Nerlynx [package insert]. Los Angeles, CA: Puma Biotechnology, Inc.
- Puma Biotechnology, Inc. Data on file.
Important Safety Information and Indications
Contraindications: None
Warnings and Precautions:
- Diarrhea: Manage diarrhea through either Nerlynx dose escalation or loperamide prophylaxis. If diarrhea occurs despite recommended prophylaxis, treat 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.
- Hepatotoxicity: Monitor liver function tests monthly for the first 3 months of treatment, then every 3 months while on treatment and as clinically indicated. Withhold Nerlynx in patients experiencing Grade 3 liver abnormalities and permanently discontinue Nerlynx in patients experiencing Grade 4 liver abnormalities.
- Embryo-Fetal Toxicity: Nerlynx can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
Adverse Reactions: The most common adverse reactions (reported in ≥5% of patients) were:
- Nerlynx as a single agent: diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increased, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased, and urinary tract infection.
- Nerlynx in combination with capecitabine: diarrhea, nausea, vomiting, decreased appetite, constipation, fatigue/asthenia, weight decreased, dizziness, back pain, arthralgia, urinary tract infection, upper respiratory tract infection, abdominal distention, renal impairment, and muscle spasms.
To report suspected adverse reactions, contact Puma Biotechnology, Inc. at 1-844-Nerlynx (1-844-637-5969) or FDA at 1-800-332-1088 or www.fda.gov/medwatch.
Drug Interactions:
- Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors. Separate Nerlynx by at least 2 hours before or 10 hours after H2-receptor antagonists. Or separate Nerlynx by at least 3 hours after antacids.
- Strong CYP3A4 inhibitors: Avoid concomitant use.
- P-gp and moderate CYP3A4 dual inhibitors: Avoid concomitant use.
- Strong or moderate CYP3A4 inducers: Avoid concomitant use.
- Certain P-gp substrates: Monitor for adverse reactions of P-gp substrates for which minimal concentration change may lead to serious adverse reactions when used concomitantly with Nerlynx.
Use In Specific Populations:
- Lactation: Advise women not to breastfeed.
Please see Full Prescribing Information.
Indications: Nerlynx® (neratinib) tablets, for oral use, is a kinase inhibitor indicated:
- As a single agent, for the extended adjuvant treatment of adult patients with early-stage HER2-positive breast cancer, to follow adjuvant trastuzumab-based therapy.
- In combination with capecitabine, for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting.