FDA Approves Neratinib for Extended Adjuvant Treatment of Early Stage HER2-Positive Breast Cancer

Approval is based on the ExteNET trial

On 17 July 2017, the US Food and Drug Administration (FDA) approved neratinib (NERLYNX, Puma Biotechnology, Inc.) for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

Approval was based on the ExteNET trial (NCT00878709), a multicentre, randomised, double-blind, placebo-controlled trial of neratinib following adjuvant trastuzumab treatment. In total, 2840 women with early-stage HER2-positive breast cancer and within two years of completing adjuvant trastuzumab were randomised to receive either neratinib (1420 patients) or placebo (1420 patients) for one year.

The major efficacy outcome measure was invasive disease-free survival (iDFS) defined as the time between the randomisation date to the first occurrence of invasive recurrence (local/regional, ipsilateral or contralateral breast cancer), distant recurrence, or death from any cause, within two years and 28 days of follow-up. After two years, iDFS was 94.2% in patients treated with neratinib compared with 91.9% in those receiving placebo (HR 0.66; 95% CI: 0.49, 0.90, p = 0.008).

The most common adverse reactions (>5%) were diarrhoea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight loss, and urinary tract infection. The most common adverse reaction leading to discontinuation was diarrhoea, observed in 16.8% of neratinib-treated patients. Hepatotoxicity or increases in liver transaminases led to drug discontinuation in 1.7% of neratinib-treated patients.

The recommended dose is 240 mg (6 tablets) given orally once daily with food, continuously for one year. Antidiarrheal prophylaxis should be initiated with the first neratinib dose and continued during the first 2 cycles (56 days) of treatment and as needed thereafter.

Full prescribing information is available here.  

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.

The results of the ExteNET study will be presented in Proffered Paper session - Breast cancer, early at forthcoming ESMO 2017 Congress in Madrid, Spain (8-12 September).