Puma Biotechnology Submits New Drug Application for HER2-Positive Breast Cancer Drug


Puma Biotechnology submitted New Drug Application (NDA) to U.S. Food and Drug Administration (FDA) for its lead candidate, PB272 (neratinib) for extended adjuvant treatment of early-stage, HER2-positive breast cancer in the patients who had received a prior adjuvant trastuzumab (Herceptin®) based therapy.

puma biotech logoIn HER2-positive breast cancer patients, cells produce excess of HER2 protein and therefore these cancer becomes aggressive and fast growing. Neratinib is a potent irreversible tyrosine kinase inhibitor. It interferes with the internal cell signalling and blocks it through human epidermal growth factor receptors, HER1, HER2 and HER4.

The NDA was supported by Phase III clinical trial (ExteNET) results of PB272 compared to placebo. The randomized 2,840 early stage HER2-positive breast cancer patients from 41 countries who had undergone surgery or adjuvant treatment with trastuzumab were included in the trial.

Neratinib chemical structure


33% reduction in the risk of invasive disease recurrence or death was seen in patients receiving neratinib compared to placebo. The invasive disease free survival (DFS) rate in 2 years in neratinib receiving patients was 93.9% compared to 91.6% in those on placebo.

neratinib pharmacology

Figure 1. Molecular mechanism of neratinib (photo credit: Breast Cancer Res. 2009. Suppl 1:S19).

In the subgroup of hormone receptor-positive (HR-positive) breast cancer patients, neratinib showed 49% reduction of risk of invasive disease recurrence or death compared to placebo and the 2-Year invasive DFS rate was 95.4% for neratinib group compared to 91.2% in those on placebo.

The Phase III trial results were later updated for 3-Year, 4-Year and an interim 5-Year invasive DFS data to analyse the long-term effect of the treatment. The results are given below.

DFS for Intent to Treat (ITT) Population

3-Year DFS 4-Year DFS 5-Year Interim DFS









Absolute invasive DFS Difference 2.2% 2.2%


For the HR-positive breast cancer subgroup, the results are given below.

DFS for Hormone Receptor Positive (HR-positive) Population

3-Year DFS 4-Year DFS 5-Year Interim DFS


93.8% 92.9%



89.9% 88.6%


Absolute invasive DFS Difference




The full 5-Year DFS data is expected to be available in 2017.

Puma in-licences the global development and marketing rights of three drug candidates- PB272 (neratinib (oral)), PB272 (neratinib (intravenous)) and PB357. The company is also exploring for the clinical application of neratinib in other types of cancer as well like non-small cell lung cancer (NSCLC).

We are very pleased to announce this important regulatory milestone,” said Alan H. Auerbach, Chief Executive Officer and President of Puma. “Although the use of trastuzumab in the adjuvant setting has led to a reduction in disease recurrence in patients with early stage HER2-positive breast cancer, there remains an unmet clinical need to further reduce the risk of recurrence and improve outcome following trastuzumab therapy. We believe that neratinib may be able to provide this type of improvement to further help patients with this disease. We look forward to working with the FDA during their review of this submission”.

Featured image credit: The uncontrolled cell proliferation leads to cancerogenesis. © animaxx3d (Stock Photo ID: 76797623)

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