The recent first global approval of neratinib has been reviewed in detail in the First Global Approval report in Adis’ journal Drugs[1], based on the development milestones tracked in AdisInsight[2].

In July 2017, neratinib (nerlynx™®), developed by Puma Biotechnology, received its first global approval in the US for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer; treatment is indicated in patients who have previously recieved trastuzumab-based therapy.[3][4] Neratinib is an oral, irreversible inhibitor of the human epidermal growth factor receptors HER1 (EGFR), HER2 and HER4. After binding, neratinib reduces the autophosphorylation of HER2 and EGFR and further inhibits the activation of downstream signal transduction pathways involved in cell cycle regulation.[1]

The National Cancer Institute estimates that 252,710 new cases of female breast cancer will be discovered in the US throughout 2017 (15% of all new cancers); of those 16% will result in death (~7% of all cancer-related deaths).[5]

Neratinib was approved based on the two-year follow-up results of the of the ExteNET trial.[6] Within two years of completing trastuzumab therapy[7], patients were randomised to neratinib or placebo for one year. The respective invasive disease-free survival rates were 94% and 92%.[4] 

Safety data from the ExteNET trial revealed that use of neratinib was associated with diarrhoea in 95% of patients receiving the agent (compared with 35% in placebo recipients); this was reported as grade 3 in 40% of cases (2% in placebo recipients).[8]Information within the product label suggests prophylactic use of loperamide during the initial cycles of neratinib.[8]

The 2% difference in the main efficacy outcome compared with the likelihood of experiencing debilitating diarrhoea has sparked some concern within the “breast cancer community” about the benefit of neratinib over and above the current treatment options.[9]

Alexandra Zimmer, M.D., of the Women’s Malignancies Branch in NCI’s Center for Cancer Research commented that, “…the modest reduction in the recurrence rate, the fact that data on overall survival are not yet available, and the high rate of side effects mean that neratinib is unlikely to be widely used by these patients.” However, she went on to explain that the agent “could be considered in patients with early-stage HER2-positive breast cancer and clinical features that indicate a higher likelihood of relapse.”[10]

Neratinib is currently under review for the same indication in the EU. [1] [2]

For further information related to the first approval of neratinib please visit Drugs[1],  or to learn more about the overall development of neratinib across all indications visit AdisInsight[2].

Image credit: florinoprea / Fotolia

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