Nerlynx (neratinib)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.


Approval Status:

Approved July 2017

Specific Treatments:

HER2 breast cancer

Therapeutic Areas

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General Information

Nerlynx (neratinib) is a kinase inhibitor that irreversibly binds to Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4.

Nerlynx is specifically indicated for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab based therapy.

Nerlynx is supplied as a tablet for oral administration. The recommended dose of Nerlynx is 240 mg (six tablets) given orally once daily with food, continuously for one year. Nerlynx should be administered at approximately the same time every day. Nerlynx tablets should be swallowed whole (tablets should not be chewed, crushed, or split prior to swallowing).  If a patient misses a dose, do not replace missed dose, and instruct the patient to resume Nerlynx with the next scheduled daily dose. Please see drug label for dose modifications based on adverse reactions.

Antidiarrheal prophylaxis with loperamide is recommended during the first 2 cycles (56 days) of treatment and should be initiated with the first dose of Nerlynx. Additional antidiarrheal agents may be required to manage diarrhea in patients with loperamide refractory diarrhea.

Clinical Results

FDA Approval

The FDA approval of Nerlynx was based on the Phase III ExteNET trial, a multicenter, randomized, double-blind, placebo-controlled trial of neratinib following adjuvant trastuzumab treatment. The trial enrolled 2,840 women with early-stage HER2-positive breast cancer and within two years of completing adjuvant trastuzumab. The subjects were randomized to receive either neratinib (n=1420) or placebo (n=1420) for one year. The results of the ExteNET trial demonstrated that after two years of follow-up, invasive disease-free survival (iDFS) was 94.2% in subjects treated with neratinib compared with 91.9% in those receiving placebo (HR 0.66; 95% CI: 0.49, 0.90, p=0.008).

Side Effects

Adverse effects associated with the use of Nerlynx may include, but are not limited to, the following:

  • 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
  • urinary tract infection

Mechanism of Action

Nerlynx (neratinib) is a kinase inhibitor that irreversibly binds to Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4. In vitro, neratinib reduces EGFR and HER2 autophosphorylation, downstream MAPK and AKT signaling pathways, and showed antitumor activity in EGFR and/or HER2 expressing carcinoma cell lines. Neratinib human metabolites M3, M6, M7 and M11 inhibited the activity of EGFR, HER2 and HER4 in vitro. In vivo, oral administration of neratinib inhibited tumor growth in mouse xenograft models with tumor cell lines expressing HER2 and EGFR. 

Additional Information

For additional information regarding Nerlynx or HER2+ breast cancer, please visit