LOS ANGELES--(BUSINESS WIRE)--Puma Biotechnology, Inc. (NYSE: PBYI), a development stage
biopharmaceutical company, announced the presentation of positive
results from the Phase III clinical trial of Puma's investigational drug
PB272 (neratinib) for the extended adjuvant treatment of breast cancer
(ExteNET trial) in patients with centrally confirmed HER2-positive early
stage breast cancer. The ExteNET trial is a double-blind,
placebo-controlled, Phase III trial of neratinib versus placebo after
adjuvant treatment with trastuzumab (Herceptin) in women with early
stage HER2-positive breast cancer. The data was presented today in an
oral presentation at the American Society of Clinical Oncology (ASCO)
2015 Breast Cancer Symposium in San Francisco, California. This data was
previously presented in June at the ASCO Annual Meeting in Chicago,
Illinois.
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 recurrent disease, ductal
carcinoma in situ (DCIS), or death for a period of two years after
randomization in the trial.
The patient characteristics in the trial were well balanced between the
neratinib and placebo arms of the trial. For the 1,420 patients in the
neratinib arm of the trial, 1,085 (76.4%) were node positive while for
the 1,420 patients in the placebo arm of the trial, 1,084 (76.3%) were
node positive. Additionally in the neratinib arm of the trial, 816
(57.5%) patients were hormone receptor positive, and in the placebo arm
of the trial, 815 (57.4%) patients were hormone receptor positive. The
median time from the last trastuzumab dose to entry into the trial was
4.4 months for the neratinib treated patients and 4.6 months for the
placebo-treated patients.
The safety results of the study showed that 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 (0.1%) patient had grade 4 diarrhea). Patients
who received neratinib in this trial did not receive any prophylaxis
with antidiarrheal agents to prevent the neratinib-related diarrhea.
Puma’s recently reported clinical data from several trials have
demonstrated that the use of high dose prophylactic loperamide greatly
reduces the rate of grade 3 diarrhea with neratinib, with grade 3
diarrhea rates ranging from 0-17% in studies in which high dose
loperamide prophylaxis was used. In all of its current ongoing studies
Puma is instituting the use of high dose loperamide for the first cycle
of treatment in order to continue to reduce the neratinib-related
diarrhea.
The primary endpoint of the trial was invasive disease free survival
(DFS). The results of the trial demonstrated that treatment with
neratinib resulted in a 33% reduction of risk of invasive disease
recurrence or death versus placebo (hazard ratio = 0.67, p = 0.009). The
2-year DFS rate for the neratinib arm was 93.9% and the 2-year DFS rate
for the placebo arm was 91.6%. As an inclusion criteria for the ExteNET
trial, patients needed to have tumors that were HER2 positive using
local assessment. In addition, as a pre-defined subgroup in the trial,
patients had centralized HER2 testing performed on their tumor as well.
To date, centralized HER2 testing has been performed on 1,705 (60%) of
the patients in the ExteNET trial and further central testing on
available samples is currently ongoing. For the 1,463 patients whose
tumors were HER2 positive by central confirmation, the results of the
trial demonstrated that treatment with neratinib resulted in a 49%
reduction of risk of invasive disease recurrence or death versus placebo
(hazard ratio = 0.51, p = 0.002). The 2-year DFS rate for the centrally
confirmed patients in the neratinib arm was 94.7% and the 2-year DFS
rate for the centrally confirmed patients in the placebo arm was 90.6%.
For the pre-defined subgroup of centrally confirmed HER2-positive
patients with hormone receptor positive disease, the results of the
trial demonstrated that treatment with neratinib resulted in a 75%
reduction of risk of invasive disease recurrence or death (hazard ratio
= 0.25, p < 0.001). The 2-year DFS rate for the centrally confirmed
patients in the neratinib arm was 97.0% and the 2-year DFS rate for
centrally confirmed patients in the placebo arm was 88.4%.
About Puma Biotechnology
Puma Biotechnology, Inc. is a development stage biopharmaceutical
company that acquires and develops innovative products for the treatment
of various forms of cancer. The Company focuses on in-licensing drug
candidates that are undergoing or have already completed initial
clinical testing for the treatment of cancer and then seeks to further
develop those drug candidates for commercial use. The Company is
initially focused on the development of PB272 (oral neratinib), a potent
irreversible tyrosine kinase inhibitor, for the treatment of patients
with HER2-positive breast cancer and patients with non-small cell lung
cancer, breast cancer and other solid tumors that have a HER2 mutation.
Further information about Puma Biotechnology can be found at www.pumabiotechnology.com.
Forward-Looking Statements:
This press release contains forward-looking statements, including, but
not limited to, statements regarding the development of our drug
candidates. All forward-looking statements included in this press
release involve risks and uncertainties that could cause the Company's
actual results to differ materially from the anticipated results and
expectations expressed in these forward-looking statements. These
statements are based on current expectations, forecasts and assumptions,
and actual outcomes and results could differ materially from these
statements due to a number of factors, which include, but are not
limited to, the fact that the Company has no product revenue and no
products approved for marketing; the Company’s dependence on PB272,
which is still under development and may never receive regulatory
approval; the challenges associated with conducting and enrolling
clinical trials; the risk that the results of clinical trials may not
support the Company’s drug candidate claims; even if approved, the risk
that physicians and patients may not accept or use the Company’s
products; the Company’s reliance on third parties to conduct its
clinical trials and to formulate and manufacture its drug candidates;
the Company’s dependence on licensed intellectual property; and the
other risk factors disclosed in the periodic reports filed by the
Company with the Securities and Exchange Commission from time to time,
including the Company’s Annual Report on Form 10-K for the year
ended December 31, 2014 and Quarterly Report on Form 10-Q for the
quarter ended June 30, 2015. Readers are cautioned not to place undue
reliance on these forward-looking statements, which speak only as of the
date hereof. The Company assumes no obligation to update these
forward-looking statements, except as required by law.
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