Nerlynx
Approved for extended adjuvant treatment of patients with early-stage HER2 overexpress/amplify breast cancer, to follow adjuvant trastuzumab based therapy.
A tyrosine kinase inhibitor targeting HER2.
ExteNET trial treated women with early-stage HER 2 positive breast cancer and within two years of completing adjuvant trastusumab or randomized to either neratinib or placebo for one year: invasive disease free survival wad 94.2% for patients treated with neratinib compared with 91.9% in those receiving placebo.
The drug lowered the risk of recurrence by 51% in HER positive patients, compared with 7% in HER negative patients.
34% reduction in risk recurrence vs placebo at 2 years.
Improves progression free survival compared with lapatinib in women with metastatic HER2 positive breast cancer who have received at least two prior regimens (NALA study).
FDA Approves sNDA for Neratinib in Combination with Capecitabine for HER2+ Breast Cancer
NALA trial demonstrated that neratinib in combination with capecitabine offers a significant improvement over currently available therapies in a heavily pretreated patient population.
In the phase III clinical trial, 621 patients were randomized 1:1 to receive either 240 mg of neratinib orally once daily on days 1-21 of the study in combination with 750 mg/m2 of capecitabine given orally twice daily on days 1-14 for each 21 day cycle (n = 307) or 1,250 mg of lapatinib (Tykerb) orally once daily on days 1-21 in combination with 1,000 mg/m2 of capecitabine given orally twice daily on days 1-14 for each 21-day cycle.
Treatment with neratinib in combination with capecitabine resulted in a statistically significant improvement in progression free survival (PFS) compared to treatment with lapatinib plus capecitabine.
The PFS rate at 12 months was 29% for patients who received neratinib plus capecitabine vs 15% for patients who received lapatinib plus capecitabine and the PFS rate at 24 months was 12%, respectively.
Effectively inhibits crosstalk between estrogen receptor and HER to pathways.
The median overall survival (OS) was 21 months for patients who received neratinib in combination with capecitabine compared to 18.7 months for those who received lapatinib in combination plus capecitabine.
The ORR was 32.8% vs 26.7% respectively, and the median duration of response was 8.5 months vs 5.6 months, respectively.
Currently, the recommended dose of neratinib for advanced or metastatic breast cancer is 240 mg (6 tablets) given orally once daily with food on days 1-21 of a 21-day cycle plus capecitabine (750 mg/m2 given orally twice daily) on days 1-14 of a 21-day cycle until disease progression or unacceptable toxicities.
It is non-cross-resistant with trastuzumab in the metastatic setting.
It crosses the blood brain barrier.
It has shown activity in brain metastases (NEfERT-T and TBCRC studies).
It reduces CNS progression, and improves outcomes when compared to standard care.
The most common adverse reactions are: diarrhea, nausea, abdominal pain, fatigue, rash, stomatitis, impaired appetite, muscle spasms, dyspepsia, increased liver functions, nail disorder, dry skin, abdominal distention, weight loss, and UTI.
There is no evidence of increased risk of long-term toxicity or long-term adverse consequences with neratinib compared with placebo.
Diarrhea is the most common side effect, severe in almost 40% of patients.
Diarrhea lead to discontinuance of the drug in 16.8% of patients.
Recommended dose 240 mg, six tablets, given orally once daily with food, continuously for one year.
Anti-diarrheal prophylaxis should be initiated with the initial treatment and as needed thereafter.