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). 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 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%.
The secondary endpoint of the trial was disease free survival including
ductal carcinoma in situ (DFS-DCIS). The results of the trial
demonstrated that treatment with neratinib resulted in a 37% reduction
of risk of disease recurrence including DCIS or death versus placebo
(hazard ratio = 0.63, p = 0.002). The 2-year DFS-DCIS rate for the
neratinib arm was 93.9% and the 2-year DFS-DCIS rate for the placebo arm
was 91.0%.
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 1,704 (60%) of the patients in the ExteNET trial, and
further central testing on available samples is currently ongoing. For
the 1,463 patients whose tumor was 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 patients in the trial
whose tumor was HER2 positive by central confirmation, the results of
the trial demonstrated that treatment with neratinib resulted in a 51%
reduction of risk of disease recurrence including DCIS or death versus
placebo (hazard ratio = 0.49, p < 0.001). The 2-year DFS-DCIS rate for
the centrally confirmed patients in the neratinib arm was 94.7% and the
2-year DFS rate for centrally confirmed patients in the placebo arm was
90.2%.
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 49% reduction of risk of invasive disease
recurrence or death versus placebo (hazard ratio = 0.51, p = 0.001). The
2-year DFS rate for the neratinib arm was 95.4% and the 2-year DFS rate
for the placebo arm was 91.2%. For the patients in the trial whose tumor
was HER2 positive by central confirmation, 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%.
“While 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 for
further improvement in outcome in order to attempt to further reduce
this risk of recurrence,” said Professor Arlene Chan, medical oncologist
at Mount Hospital and the Vice Chair of the Breast Cancer Research
Centre WA. “The results of the ExteNET study demonstrate that we may be
able to provide this type of improvement with neratinib to further help
the patients with this disease.”
“We are very pleased with the results of the ExteNET trial with
neratinib. This represents the first trial with a HER2 targeted agent
that has shown a statistically significant 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,” said Alan H. Auerbach, Chief Executive Officer and President of
Puma. “We are also intrigued by the activity in the hormone receptor
positive subgroup of patients, which we believe may be the result of
neratinib inhibiting the cross talk between the estrogen receptor and
the HER2 receptor and which may help the tumor increase its sensitivity
to endocrine therapy. We look forward to proceeding with the regulatory
filing for neratinib for the extended adjuvant treatment of breast
cancer currently anticipated in the first quarter of 2016.”
Webcast
The Company will host a meeting and webcast to discuss the results of
the Phase III ExteNET trial beginning at approximately 7:00 p.m. CDT
(8:00 p.m. EDT) on Monday, June 1, 2015. The webcast will be accessible
through the Investor Relations section of Puma’s website at http://www.pumabiotechnology.com/ir_events.html
and will be archived there for 30 days.
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 and the anticipated timing of regulatory filings. 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. 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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