by Dr. C.H. Weaver M.D. updated 2/20
The U.S. Food and Drug Administration has approved Nerlynx (neratinib) for the extended adjuvant treatment of adult patients with early stage HER2 - overexpressed/amplified breast cancer, to follow adjuvant Herceptin (trastuzumab)-based therapy and for use in patients with metastatic breast cancer.
Nerlynx is a novel tyrosine kinase inhibitor that is targeted against several biochemical pathways implicated in the growth and spread of cancer. Specifically, Nerlynx is targeted against the HER1, HER2, and HER4 pathways and was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-positive breast cancer following adjuvant trastuzumab-based therapy.
Nerlynx Improves Cancer-Free Survival in Early Breast Cancer
The targeted agent Nerlynx demonstrated an improvement in cancer-free survival when used after Herceptin® in early-stage, HER2-positive breast cancer.
Approximately 20-30% of breast cancer is referred to as human epidermal growth factor receptor-2 (HER2)-positive. This means that the breast cancer cells have too many HER2 proteins on their surface, which stimulates the cancer cells to grow and spread.
Agents targeting the HER2 proteins and HER2 pathway have been approved for the treatment of HER2-positive breast cancers. These agents reduce the excessive biochemical signaling that stimulates cancer growth and spread in HER2-positive cancers.
Herceptin is a commonly used agent in breast cancer that is targeted against HER2 proteins. It has demonstrated improvements in outcomes among patients with HER2-positive breast cancers, including early-stage breast cancers.
Neratinib is a novel agent referred to as a tyrosine kinase inhibitor that is targeted against several biochemical pathways implicated in the growth and spread of cancer. Specifically, Nerlynx is targeted against the HER1, HER2, and HER4 pathways.
The exteNET clinical trial, included 2,840 patients from 41 countries with HE2-positive early breast cancer who had received treatment with surgery, followed by treatment including Herceptin.
Following the completion of therapy with Herceptin, one group of patients in the trial received further treatment with Nerlynx, while the other group of patients received placebo (inactive substitute) for one year.
- Among patients treated with Nerlynx, survival rates without an invasive recurrence of cancer were as follows: approximately 94% at 2 years; 92.5% at 3 years; 91.4% at 4 years; and 90.4% at 5 years.
- Among patients who received placebo, the survival rates without an invasive recurrence of cancer were as follows: 91.6% at 2 years; 90.3% at 3 years; 89.2% at 4 years; 87.9% at 5 years.
Among the group of patients with hormone-receptor positive (HR-positive) breast cancer (meaning the patient’s breast cancer is stimulated to grow from exposure to the female hormones estrogen and/or progesterone), the survival rates without an invasive recurrence of cancer were as follows:
- 8% at 3 years; 92.9% at 4 years; and 91.7% at 5 years among those who were treated with Nerlynx
- 9% at 3 years; 88.6% at 4 years; and 86.9% at 5 years among those who received placebo.
These results indicate that Nerlynx improves survival without a recurrence of invasive cancer among patients with early-stage, HER2-positive breast cancer who have completed treatment with surgery and Herceptin.
Nerlynx Improves Cancer-Free Survival in Advanced Breast Cancer
The international NALA clinical trial included 621 patients with metastatic HER2-positive breast cancer who received ≥2 previous prior anti-HER2–based treatment regimens. Patients were treated with either Nerlynx 240 mg once daily on days 1 through 21 plus Xeloda 750 mg/m2 twice daily on days 1 to 14 of each 21-day cycle or Tykerb 1250 mg once daily on days 1 through 21 plus Xeloda 1000 mg/m2 twice daily on days 1 to 14 of each 21-day and directly compared.
Patients who received Nerlynx plus Xeloda were more likely to respond to respond to treatment, live longer and experience improvement in survival without cancer progression compared to those given Tykerb plus Xeloda. The 24-month survival without progression rate was 12% versus 3% respectively. (5)
The most common adverse reactions were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, nail disorder, dry skin, abdominal distention, weight loss, and urinary tract infection. The most common adverse reaction leading to discontinuation was diarrhea, observed in 16.8% of 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 Nerlynx dose and continued during the first 2 cycles (56 days) of treatment and as needed thereafter.
- Puma Biotech Inc. News Release. Puma Biotechnology Announces Interim 5-Year Disease Free Survival Data from Phase III Trial of PB272 (Neratinib) in Extended Adjuvant HER2-Positive Early Stage Breast Cancer (ExteNET Trial). Available at: http://www.pumabiotechnology.com/pr20160721_2.html. Accessed July 25, 2016.
- Burstein HJ, Sun Y, Dirix LY et al. Neratinib, an irreversible ErbB Receptor tyrosine kinase inhibitor, in patients with advanced ErbB2-positive breast cancer. Journal of Clinical Oncology. 2010; 28: 1301-1307.
- Puma Biotechnology Receives U.S. FDA Approval of Supplemental New Drug Application for Nerlynx to Treat HER2-Positive Metastatic Breast Cancer [news release]. Los Angeles, CA: Puma Biotechnology; February 26, 2020. www.biospace.com/article/releases/puma-biotechnology-receives-u-s-fda-approval-of-supplemental-new-drug-application-for-Nerlynx-to-treat-her2-positive-metastatic-breast-cancer. Accessed February 26, 2020.