Class/mechanism: Irreversible pan-ErbB tyrosine kinase inhibitor of HER2 (human epidermal growth factor receptor 2), EGFR (epidermal growth factor receptor), and ERBB4. Neratinib inhibits activity and downstream signalling of the tyrosine kinase domains of these receptors, likely by interacting with cysteine residue in their ATP-binding pockets. This inhibition has been observed to cause cell cycle arrest in the G1-S (Gap 1/DNA synthesis) phase of the cell division cycle.
For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the package insert.
Diseases for which it is used
Patient drug information
History of changes in FDA indication
- 2017-07-17: FDA approved for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy. (Based on ExteNET)
- 2020-02-25: Approved in combination with capecitabine for 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. (Based on NALA)
History of changes in EMA indication
- 2018-08-31: Initial authorization
History of changes in Health Canada indication
- 2019-07-16: Initial notice of compliance for the extended adjuvant treatment of women with early-stage hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-overexpressed/amplified breast cancer within one year after completion of trastuzumab-based adjuvant therapy.
- 2021-06-23: New indication (unclear details)
Also known as
- Code name: HKI-272
- Brand name: Nerlynx
- ↑ 1.0 1.1 1.2 Neratinib (Nerlynx) package insert
- ↑ Neratinib (Nerlynx) package insert (locally hosted backup)
- ↑ Nerlyn manufacturer's website
- ↑ Rabindran SK, Discafani CM, Rosfjord EC, Baxter M, Floyd MB, Golas J, Hallett WA, Johnson BD, Nilakantan R, Overbeek E, Reich MF, Shen R, Shi X, Tsou HR, Wang YF, Wissner A. Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res. 2004 Jun 1;64(11):3958-65. link to original article PubMed