- How Much We Know About Breast cancer?
- Clinical Results By FDA Apprvoal
- What Is Neratinib?
- Who Might Need Neratinib?
- How To Know Whether Neratinib Is Right For You?
- How Does Neratinib Works?
- How We Take Neratinib?
- What We May See Side Effects Of Neratinib?
How Much We Know About Breast cancer?
Breast cancer is the most common type of cancer in women, representing 15% of all new cancer cases in the United States. In 2017, 252,710 new cases of breast cancer were estimated to be diagnosed, and more than 40,600 women to die from the disease. Breast cancer can also, rarely, affect men, with approximately 2470 new cases diagnosed annually.
Approximately 15% to 20% of breast cancer tumors are HER2-positive. Breast cancers with high levels of HER2 have an increased risk for metastasis, inadequate treatment response, and recurrence.
The development and subsequent US Food and Drug Administration (FDA) approval of trastuzumab (Herceptin), a HER2 receptor antagonist, changed the treatment paradigm for patients with HER2-positive disease. When trastuzumab was added to chemotherapy, the overall survival rates for women with early-stage HER2-positive breast cancer improved by up to 37%. However, approximately 26% of patients have recurrent disease after treatment with trastuzumab.
Other therapies that target HER2-positive breast cancer include pertuzumab (Perjeta), a monoclonal antibody; ado-trastuzumab emtansine (Kadcyla), a monoclonal antibody attached to a chemotherapy drug; and lapatinib (Tykerb), a kinase inhibitor.
Clinical Results By FDA Apprvoal
The FDA approval of Neratinib was based on the Phase III ExteNET trial, a multicenter, randomized, double-blind, placebo-controlled trial of neratinib following adjuvant trastuzumab treatment. The trial enrolled 2,840 women with early-stage HER2-positive breast cancer and within two years of completing adjuvant trastuzumab. The subjects were randomized to receive either neratinib (n=1420) or placebo (n=1420) for one year. The results of the ExteNET trial demonstrated that after two years of follow-up, invasive disease-free survival (iDFS) was 94.2% in subjects treated with neratinib compared with 91.9% in those receiving placebo.
Neratinib was also evaluated in the Phase III NALA trial, a randomized controlled trial of neratinib plus capecitabine in patients with HER2-positive metastatic breast cancer who have received two or more prior anti-HER2-based regimens. The trial enrolled 621 patients who were randomized (1:1) to receive neratinib 240 mg orally once daily on days 1-21 in combination with capecitabine 750 mg/m2 given orally twice daily on days 1-14 for each 21-day cycle (n=307) or lapatinib 1250 mg orally once daily on days 1-21 in combination with capecitabine 1000 mg/m2 given orally twice daily on days 1-14 for each 21-day cycle (n=314). Patients were treated until disease progression or unacceptable toxicity. 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; the PFS rate at 24 months was 12% vs 3%, respectively. Median OS was 21 months for patients who received neratinib in combination with capecitabine compared to 18.7 months for patients who received lapatinib in combination plus capecitabine.
What Is Neratinib?
Neratinib(CAS: 698387-09-6) is a targeted (biological) therapy drug that blocks the growth and spread of breast cancer. Neratinib is the drug’s non-branded name. Its brand name is Nerlynx.
Who Might Need Neratinib?
Neratinib may be offered to people who have primary breast cancer that is both:
❶ Hormone receptor positive (breast cancer that’s stimulated to grow by the hormones oestrogen or progesterone)
❷ HER2 positive (breast cancer that has a higher than normal level of the HER2 protein)
How To Know Whether Neratinib Is Right For You?
There are several tests used to find out if breast cancer is HER2-positive. Two of the most common tests are:
❶ IHC (ImmunoHistoChemistry)
The IHC test uses a chemical dye to stain the HER2 proteins. The IHC gives a score of 0 to 3+ that measures the amount of HER2 proteins on the surface of cells in a breast cancer tissue sample. If the score is 0 to 1+, it’s considered HER2-negative. If the score is 2+, it’s considered borderline. A score of 3+ is considered HER2-positive.
If the IHC test results are borderline, it’s likely that a FISH test will be done on a sample of the cancer tissue to determine if the cancer is HER2-positive.
❷ FISH (Fluorescence In Situ Hybridization)
The FISH test uses special labels that are attached to the HER2 proteins. The special labels have chemicals added to them so they change color and glow in the dark when they attach to the HER2 proteins. This test is the most accurate, but it is more expensive and takes longer to return results. This is why an IHC test is usually the first test done to see if a cancer is HER2-positive. With the FISH test, you get a score of either positive or negative (some hospitals call a negative test result “zero” ).
How Does Neratinib Works?
HER2-positive breast cancers make too much of the HER2 protein. The HER2 protein sits on the surface of cancer cells and receives signals that tell the cancer to grow and spread. About one out of every four breast cancers is HER2-positive. HER2-positive breast cancers tend to be more aggressive and harder to treat than HER2-negative breast cancers. Neratinib is an irreversible pan-HER inhibitor. Neratinib fights HER2-positive breast cancer by blocking the cancer cells’ ability to receive growth signals.
Neratinib is a targeted therapy, but unlike Herceptin (chemical name: trastuzumab), Kadcyla (chemical name: T-DM1 or ado-trastuzumab emtansine), and Perjeta (chemical name: pertuzumab), it is not an immune targeted therapy. Immune targeted therapies are versions of naturally occurring antibodies that work like antibodies made by our immune systems. Neratinib is a chemical compound, not an antibody.
How We Take Neratinib?
The recommended dose of neratinib is 240 mg (6 tablets), taken orally once daily with food, and used continuously for 1 year. Neratinib is available as a 40-mg tablet.
For antidiarrheal prophylaxis, loperamide should be used concomitantly with the first dose of neratinib and continued during the first 2 cycles (ie, 56 days) of treatment, and then as needed. Patients should be instructed to maintain 1 to 2 bowel movements daily, and should be instructed on how to use antidiarrheal treatment regimens.
Specific dose interruption and/or dose reduction recommendations, based on the patient’s individual tolerability, are outlined in the prescribing information. For patients with severe hepatic impairment, the starting neratinib dose should be reduced to 80 mg.
Noted: all datas was only as reference, from NERLYNX (neratinib) tablets(PDF)
What We May See Side Effects Of Neratinib?
Severe diarrhea soon after starting neratinib is a very common side effect. In the ExteNET trial, about 40% of the women treated with neratinib had severe diarrhea as a side effect.
The FDA approval recommends that loperamide (brand names include Imodium, Kaopectate 1-D, and Pepto Diarrhea Control) be given with neratinib for the first 56 days of treatment and then as needed to help manage diarrhea.
Other common side effects of neratinib are:
▪ abdominal pain
▪ mouth sores
In rare cases, neratinib may cause serious liver problems. Tell your doctor right away if you have any of the following signs of liver problems:
▪ yellowing of the skin or the whites of the eyes
▪ dark or brown urine
▪ feeling very tired
▪ loss of appetite
▪ pain on the upper right side of the abdomen
▪ bleeding or bruising more easily than normal
The FDA approval of neratinib, an oral kinase inhibitor, marked the availability of the first extended adjuvant treatment option for appropriate patients with early-stage, HER2-positive breast cancer. Patients with HER2-positive breast cancer who received neratinib for 1 year achieved a significantly improved 2-year invasive disease-free survival compared with patients who received placebo, after chemotherapy and trastuzumab-based adjuvant therapy.
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 National Cancer Institute. Male breast cancer treatment (PDQ)–health professional version. Updated May 25, 2017. www.cancer.gov/types/breast/hp/male-breast-treatment-pdq. Accessed September 22, 2017.