Survival Data Presented From Phase II Study of Investigational Drug ZD4054 in Hormone-Resistant Prostate Cancer Patients
Wide-Ranging ZD4054 Phase III Development Program
Announced
WILMINGTON, Del., Sept. 25 /PRNewswire-FirstCall/ -- The results
from the randomized, double-blind, placebo-controlled, Phase II
EPOC (Endothelin A Proof Of Concept) Study of ZD4054 -- a specific
endothelin A (ETA) receptor antagonist -- were delivered today at
the 14th European Congress of Clinical Oncology (ECCO, 23-27
September, Barcelona). The data presented today for ZD4054, an
investigational compound in development for the treatment of men
with hormone resistant prostate cancer (HRPC), showed no
differences in progression free survival (PFS) but did report
encouraging overall survival (OS) data.(1)
To further evaluate the potential of ZD4054, the Phase III trial
program ENTHUSE (ENDOTHELIN A USE), consisting of three studies,
will begin this year. The first of these trials is aimed at
investigating the efficacy of ZD4054 in metastatic HRPC, while the
second will look at its role in nonmetastatic HRPC patients. A
third trial will study ZD4054 in combination with docetaxel
(Taxotere(TM)) for the treatment of metastatic HRPC.
Nick James, Professor of Clinical Oncology, Institute for Cancer
Studies, Birmingham, UK, and principal investigator of the EPOC
study said: "Men with advanced prostate cancer are typically
treated with hormonal therapies. Whilst these therapies can provide
great benefits, most men will become resistant to them. Currently,
the only licensed treatment option for metastatic patients shown to
improve survival in men with HRPC is chemotherapy with
docetaxel."
"The results from the EPOC study suggest that ZD4054 10 mg once
daily may have the potential to increase the median overall
survival time for men with asymptomatic or mildly symptomatic
metastatic HRPC."
EPOC (Endothelin A Proof Of Concept) Phase II findings:
The primary endpoint of the study was progression free survival
(PFS) and a secondary endpoint was Overall Survival (OS). The PFS
data did not show a statistically significant difference between
ZD4054 and placebo treatment arms. The updated Phase II data
presented today show that, patients who received ZD4054 10 mg once
daily had a median OS of 24.5 months, patients who received ZD4054
15 mg once daily had a median OS of 23.5 months and the placebo arm
had a median OS of 17.3 months.
The side effect profile of ZD4054 in this study included headache,
edema and nasal congestion.
The OS results were as follows:
Intent-to-treat population ZD4054 15mg ZD4054 10mg Placebo
Number of patients 98 107 107
Number of deaths 34 33 51
Median overall survival (months) 23.5 24.5 17.3
Hazard ratio versus placebo 0.65 0.55 -
80% CI 0.49, 0.86 0.41, 0.73 -
"It is usual to use PFS as an endpoint in Phase II studies, however
it can be difficult to measure accurately in patients with
metastatic HRPC. Overall survival is an unambiguous endpoint and
clearly an important outcome for patients," commented Professor
Nick James.
PFS in this study was measured through clinical or radiological
evidence of disease worsening, or worsening of disease-related
pain. However, patients with metastatic HRPC can typically have
multiple bone metastases, making assessments of further changes in
bone metastases difficult.
The Phase II EPOC study design:
This study recruited a total of 312 asymptomatic or mildly
symptomatic HRPC patients with bone metastases who were randomized
into one of three treatment arms: 15 mg ZD4054 once daily; 10 mg
ZD4054 once daily or a placebo tablet once daily. In addition to
study treatment, all men randomized into the study received best
supportive care.
Mode of action -- specific ETA receptor antagonism:
ZD4054 targets the ETA receptor. Inhibition of this receptor is
thought to be related to multiple processes that drive tumour
growth and spread, including tumour cell proliferation, tumour cell
survival, angiogenesis, and the formation of bone
metastases.(2)
Notes to Editors
About Prostate Cancer
Prostate cancer primarily affects men over the age of 50.(3) It is
the most commonly diagnosed male cancer in many western countries
and its incidence is increasing. Worldwide, more than 670,000 men
are diagnosed with prostate cancer every year, accounting for one
in nine of all new cancers in men. Prostate cancer is the second
most common cancer in men after lung cancer.(4) HRPC affects
approximately 60,000 new patients in the US alone each
year.(5)
About AstraZeneca
AstraZeneca is a major international health care business engaged
in the research, development, manufacture and marketing of
prescription pharmaceuticals and the supply of health care
services. It is one of the world's leading pharmaceutical companies
with health care sales of $26.475 billion and leading positions in
sales of gastrointestinal, cardiovascular, neuroscience,
respiratory, oncology, and infection products. AstraZeneca is
listed in the Dow Jones Sustainability Index (Global) as well as
the FTSE4 Good Index.
For more information visit:
http://www.astrazeneca-us.com
http://www.prostateinfo.com
References:
(1) James, M.D. ZD4054, a potent, specific endothelin A receptor
antagonist, improves overall survival in pain-free or mildly
symptomatic patients with hormone-resistant prostate cancer (HRPC)
and bone metastases.
(2) Morris, C.D. et al. Specific inhibition of the endothelin A
receptor with ZD4054: clinical and pre-clinical evidence. British
Journal of Cancer. 2005: 92
(3) Kirby RS et al. Prostate cancer and sexual function. Prostate
Cancer and Prostatic Diseases 1998:1:179-184.
(4) Cancer Research UK, Prostate Cancer Incidence statistics
http://info.cancerresearchuk.org/cancerstats/types/prostate/incidence/.
(5) DaVinci Cancer!MPact 2006.
SOURCE AstraZeneca
Posted: September 2007
