Puma Biotechnology is seeking FDA approval for a new indication for neratinib (Nerlynx) in human epidermal growth receptor 2 (HER2)-positive metastatic breast cancer, according to a press release.
 
Neratinib was initially approved in July 2017 as an extended adjuvant treatment for adults with early-stage HER2-overexpressed/amplified breast cancer following adjuvant trastuzumab-based therapy. Officials with the FDA have now accepted Puma’s supplemental New Drug Application (sNDA) for use of neratinib in combination with capecitabine for the third-line treatment of patients with HER2-positive metastatic disease.
 
In breast cancer, approximately 20% to 25% of tumors over-express the HER2 protein, which can result in more aggressive disease, according to Puma. Although trastuzumab has been shown to reduce the risk of early stage HER2-positive breast cancer returning after surgery, 25% of patients still experience recurrence, indicating a need for new treatment options for this population.
 
The sNDA is based on data from the phase 3 NALA trial, which evaluated neratinib plus capecitabine versus lapatinib (Tykerb) plus capecitabine in 621 patients with third-line HER2-positive metastatic breast cancer. Co-primary endpoints of the trial included centrally confirmed progression-free survival (PFS) and overall survival (OS).
 
For the primary endpoints, the results showed:
  • In a prespecified analysis, the mean PFS for patients treated with neratinib plus capecitabine was 8.8 months compared with 6.6 months in patients treated with lapatinib plus capecitabine.
  • The median OS for patients who received neratinib plus capecitabine was 21 months compared with 18.7 months in patients treated with lapatinib plus capecitabine, according to the study.
  • In a prespecified restricted means analysis, the mean OS at 48 months in patients treated with neratinib plus capecitabine was 24 months and the mean OS for patients treated with lapatinib plus capecitabine was 22 months. 
Results from the secondary endpoint analyses showed:
  • The overall cumulative incidence for intervention for central nervous system metastases was 22.8% of patients for the neratinib plus capecitabine arm and 29.2% of patients for the lapatinib plus capecitabine arm.
  • Neratinib plus capecitabine resulted in a longer duration of response compared with lapatinib and capecitabine, with a median response of 8.54 months compared with 5.55 months, respectively.
 Overall, treatment-emergent adverse events were similar between both treatment arms.
 
The FDA has set an action date of late April 2020, according to the press release. In addition to accepting this sNDA, the FDA has granted Orphan Drug Designation to neratinib for the treatment of patients with breast cancer who have brain metastases.
 
References
 
Puma Biotechnology Announces US FDA Acceptance of Supplemental New Drug Application for Neratinib to Treat HER2-Positive Metastatic Breast Cancer [news release]. Puma. https://www.pumabiotechnology.com/pr20190911.html. Accessed September 13, 2019.
 
Puma Biotechnology Submits a Supplemental New Drug Application to US FDA for Neratinib to Treat HER2-Positive Metastatic Breast Cancer [news release]. Puma. https://www.pumabiotechnology.com/pr20190701.html, Accessed September 13, 2019.