Neratinib

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Structural formula
Structural formula of neratinib
General
Non-proprietary name Neratinib
other names

(2 E ) - N - [4 - [[3-Chloro-4 - [(pyridin-2-yl) methoxy] phenyl] amino] -3-cyano-7-ethoxyquinolin-6-yl] -4- (dimethylamino ) but-2-enamide

Molecular formula C 30 H 29 Cl 1 N 6 O 3
External identifiers / databases
CAS number 698387-09-6
EC number 811-237-1
ECHA InfoCard 100.241.512
PubChem 9915743
ChemSpider 8091392
DrugBank DB11828
Wikidata Q6995920
Drug information
ATC code

L01 XE45

Drug class

Protein kinase inhibitors , tyrosine kinase inhibitors

properties
Molar mass 557.04 g mol −1
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Neratinib (formerly HKI-272), (trade name: Nerlynx ; distributor: Pierre Fabre ) is a drug from the group of tyrosine kinase inhibitors that is used to treat breast cancer in the early stages after surgery to reduce the risk of the disease coming back ( Relapse ). Neratinib is used after treatment with trastuzumab ( Herceptin ; a medicine used for the same purpose).

The US Food and Drug Administration (FDA) approved neratinib in July 2017 . The European Commission granted EU approval in August 2018.

Clinical information

application areas

Neratinib / Nerlynx is suitable ( indicated ) for the extended adjuvant treatment of adult patients with hormone receptor-positive HER2-overexpressed / amplified breast cancer at an early stage who completed trastuzumab-based adjuvant therapy less than a year ago.

It is only for use in breast cancer, which produces high levels of a protein called HER2 that helps cells divide and grow (HER2-positive breast cancer) and which also has receptors (targets) for female sex hormones ( Hormone receptor positive breast cancer).

unwanted effects

The medicine is subject to additional monitoring. This enables new security knowledge to be identified quickly.

The most common side effects of any severity were diarrhea (93.6%), nausea (42.5%), fatigue (27.3%), vomiting (26.8%), abdominal pain (22.7%), rash (15.4%), loss of appetite (13.7%), upper abdominal pain (13.2%), stomatitis (11.2%) and muscle spasms (10.0%). It may be either severe diarrhea, which with dehydration ( dehydration is associated). Diarrhea usually occurs early in the first or second week of treatment with Nerlynx and can recur.

Patients should take precautionary diarrhea treatment (e.g., loperamide ) with the first dose of Nerlynx at the start and during the first 1-2 months of Nerlynx treatment so that a frequency of 1-2 bowel movements per day is achieved. Treatment of diarrhea requires the correct use of diarrhea medication, dietary changes, and an appropriate change in Nerlynx dose. The high side effect rates (diarrhea) are among other things. a. also due to the fact that in the registration study ExteNET (see below) a preventive diarrhea treatment was not prescribed.

Special patient groups

Elderly patients (≥ 65 years of age) have an increased risk of renal failure and dehydration, which can be a complication of diarrhea. Therefore, these patients should be carefully monitored. Patients with chronic gastrointestinal disease and diarrhea as a major symptom should be carefully monitored.

Pharmacological properties

Mechanism of action

Neratinib binds to the HER2 protein on cancer cells, blocking its effect. Because HER2 helps cells grow and divide, blocking the protein will help keep these cells from growing and prevent the cancer from recurring.

Absorption and distribution in the body

Absorption after oral administration of 240 mg was slow and peak plasma concentrations of neratinib occurred about 7 hours after administration.

Registration study

  • ExteNET (NCT00878709): Nerlynx was shown to be more effective than placebo (a dummy treatment) at preventing breast cancer from coming back in a main study involving 2,840 women with HER2-positive early-stage breast cancer who had already received trastuzumab. Around 94% of women who received one year of treatment with Nerlynx lived an additional year after stopping Nerlynx treatment without the cancer coming back, compared with 92% of those who received placebo. When only women with hormone receptor positive cancer were included, 95% of those given Nerlynx lived another year without the cancer coming back, compared with 91% of those given placebo.

literature

  • José Baselga, Robert E. Coleman, Javier Cortés and Wolfgang Jannid: Advances in the management of HER2-positive early breast cancer In: Crit Rev Oncol Hematol Volume 119, December 2017, pp. 113-122, doi: 10.1016 / j.critrevonc .2017.10.001 . PMID 29042085 .
  • Arlene Chan, Suzette Delaloge, Frankie A Holmes, Beverly Moy, Hiroji Iwata, Vernon J Harvey et al .: Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomized, double-blind , placebo-controlled, phase 3 trial In: The Lancet Oncology Volume 17, Number 3, February 2016, pp. 367-377, doi: 10.1016 / S1470-2045 (15) 00551-3 .
  • Ernst Mutschler et al .: Mutschler - drug effects textbook of pharmacology and toxicology . 10th edition. Scientific Verlagsgesellschaft, Stuttgart 2012, ISBN 978-3-8047-2898-1 .

Individual evidence

  1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  2. ↑ FDA approves neratinib for extended adjuvant treatment of early stage HER2-positive breast cancer , PM FDA of July 17, 2017, accessed on October 28, 2019.
  3. ↑ a b c d Summary of Product Characteristics , EMA EPAR, accessed on October 28, 2019.
  4. ↑ Nerlynx Neratinib , EMA EPAR, accessed on October 28, 2019.
  5. ↑ Overview of Nerlynx and rationale for approval in the EU , EMA, accessed on October 28, 2019.
  6. ↑ Puma Biotechnology Presents Interim Results of Phase II CONTROL Trial of Neratinib in Extended Adjuvant Treatment of HER2-Positive Early Stage Breast Cancer at the ASCO 2019 Annual Meeting ( Memento November 4, 2019 in the Internet Archive ), PM Puma Biotechnology June 2 2019, accessed November 4, 2019
  7. ↑ Prof. Miguel Martin, MD Frankie A Holmes, MD Bent Ejlertsen, MD Suzette Delaloge, MD Beverly Moy, MD Hiroji Iwata, MD et al .: Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5 -year analysis of a randomized, double-blind, placebo-controlled, phase 3 trial In: The Lancet Oncology Volume 18, number 12, December 2017, pp. 1688–1700, doi: 10.1016 / S1470-2045 (17) 30717- 9 . PMID 29146401 .

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