On November 13, 2017 Puma Biotechnology, Inc. (Nasdaq: PBYI), a biopharmaceutical company, reported the publication of previously presented results from the ExteNET Phase III clinical trial of Puma’s drug neratinib in patients with early stage HER2-positive breast cancer in the journal The Lancet Oncology (Press release, Puma Biotechnology, NOV 13, 2017, View Source [SID1234522009]).

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The article, entitled "Neratinib after trastuzumab-based adjuvant therapy in early stage HER2-positive breast cancer (ExteNET): 5-year analysis of a randomized, double blind, placebo-controlled phase III trial," appears in the November 13th online issue of The Lancet Oncology and will be published in a future print issue of the journal.

The ExteNET trial is a double-blind, placebo-controlled, Phase III trial of neratinib versus placebo after adjuvant treatment with trastuzumab (Herceptin) in patients with early stage HER2-positive breast cancer. The predefined 5-year invasive disease free survival (iDFS) analysis as a follow-up to the primary 2-year iDFS analysis of the Phase III ExteNET trial was published online today.

The ExteNET trial randomized 2,840 patients in 41 countries with early stage HER2-positive breast cancer who had undergone surgery and adjuvant treatment with trastuzumab. After completion of adjuvant treatment with trastuzumab, patients were randomized to receive extended adjuvant treatment with either neratinib or placebo for a period of one year. Patients were then followed for invasive recurrent disease, ductal carcinoma in situ (DCIS), or death for a period of five years after randomization in the trial.

Neratinib 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, and is marketed in the United States as NERLYNX (neratinib) tablets.

The primary endpoint of the trial was invasive disease free survival (iDFS). The results of the trial demonstrated that after a median follow up of 5.2 years, treatment with neratinib resulted in a 27% reduction of risk of invasive disease recurrence or death versus placebo (hazard ratio = 0.73, p = 0.008). The 5-year iDFS rate for the neratinib arm was 90.2% and the 5-year iDFS rate for the placebo arm was 87.7%.

The secondary endpoint of the trial was invasive disease free survival including ductal carcinoma in situ (iDFS-DCIS). The results of the trial demonstrated that treatment with neratinib resulted in a 29% reduction of risk of disease recurrence including DCIS or death versus placebo (hazard ratio = 0.71, p = 0.004). The 5-year iDFS-DCIS rate for the neratinib arm was 89.7% and the 5-year iDFS-DCIS rate for the placebo arm was 86.8%.

For the pre-defined subgroup of patients with hormone receptor positive disease, the results of the trial demonstrated that treatment with neratinib resulted in a 40% reduction of risk of invasive disease recurrence or death versus placebo (hazard ratio = 0.60, p = 0.002). The 5-year iDFS rate for the neratinib arm was 91.2% and the 5-year iDFS rate for the placebo arm was 86.8%. For the pre-defined subgroup of patients with hormone receptor negative disease, the results of the trial demonstrated that treatment with neratinib resulted in a hazard ratio of 0.95 (p = 0.762).

"ExteNET represents the first trial with a HER2-targeted agent that has shown a benefit in the extended adjuvant setting, which we believe provides a meaningful point of differentiation for neratinib in the treatment of HER2-positive breast cancer. We are pleased that The Lancet Oncology has chosen to publish these results," said Alan H. Auerbach, Chief Executive Officer and President of Puma.

The safety results were unchanged from the primary 2-year iDFS analysis of the study that showed the most frequently observed adverse event for the neratinib-treated patients was diarrhea, with approximately 39.9% of the neratinib-treated patients experiencing grade 3 or higher diarrhea (1 patient (0.1%) had grade 4 diarrhea). No evidence of increased risk of long-term toxicity or long-term adverse consequences of neratinib-associated diarrhea were identified in the analysis. Patients who received neratinib in this trial did not receive any prophylaxis with antidiarrheal agents to prevent the neratinib-related diarrhea. Puma is currently running the ongoing CONTROL trial to investigate the use of loperamide-based prophylaxis to reduce the incidence of grade 3 or higher diarrhea in patients with early stage HER2-positive breast cancer who have completed adjuvant trastuzumab-based treatment. The most recently reported clinical data from CONTROL in June 2017 demonstrated that the use of loperamide-based prophylaxis reduced the rate of grade 3 diarrhea with neratinib, with grade 3 diarrhea rates ranging from 8-31% when loperamide-based prophylaxis was used.