BEERSE, Belgium–([HR])–Janssen-Cilag International NV today announced data from the pivotal
Phase 3 LATITUDE clinical trial, which showed Zytiga®
(abiraterone acetate) plus prednisone, in combination with androgen
deprivation therapy (ADT), compared to ADT plus placebo, demonstrated a
significant improvement in overall survival (OS) and radiographic
progression-free survival (rPFS) in patients with newly diagnosed
high-risk metastatic hormone-naïve prostate cancer (mHNPC) (patients who
had not been previously treated with ADT).1 These data were
selected as one of four data sets for inclusion in the 2017 American
Society of Clinical Oncology (ASCO) Annual Meeting Press Program in
Chicago, today at 8 – 9 a.m. CDT. Additionally, the data results will be
presented during the “Plenary Session: Including the Science of Oncology
Award and Lecture,” on Sunday, 4th June, at 2:40 – 2:55 p.m.
CDT (Abstract LBA3). The data have been selected for “Best of ASCO”
Meetings, which highlight the most cutting-edge science and education
from the ASCO Annual Meeting, and reflect the foremost oncology research
and strategies that will directly impact patient care.
Study findings indicated that treatment with abiraterone acetate plus
prednisone, in combination with ADT, reduced the risk of death by 38%
compared to ADT and placebo (hazard ratio [HR]=0.62; 95% CI [0.51 to
0.76], pThis is important new information, as not all
patients respond well to the current standard of care. LATITUDE suggests
that abiraterone acetate plus prednisone, in combination with androgen
deprivation therapy, can offer a new and much-needed option for patients
with high-risk newly diagnosed mHNPC.”
There are approximately 420,000 men diagnosed with prostate cancer in
Europe per year.2 Around 2%-43% (up to 180,000) have
metastatic prostate cancer.3,4,5 Historically, ADT and
docetaxel have been the standard of care for patients with metastatic
prostate cancer. This is often very effective at shrinking or slowing
the growth of prostate cancer that has spread, but it usually becomes
less effective over time.6,7,8
In addition to achieving significant improvement on both primary
endpoints of OS and rPFS, the LATITUDE study met all secondary
endpoints, with statistically significant improvements in the
abiraterone acetate plus prednisone arm for time to: pain progression,
initiation of next subsequent therapy for prostate cancer, initiation of
chemotherapy, prostate-specific antigen (PSA) progression (all
pJanssen has played an important role in addressing treatment
challenges and transforming the way metastatic prostate cancer is
managed over the past seven years. We are very excited to see the
positive LATITUDE data results for abiraterone acetate plus prednisone
in hormone-naïve metastatic prostate cancer. These data have served the
basis for our submission to the European Medicines Agency (EMA) to
expand the use of abiraterone acetate plus prednisone to include an
earlier stage of prostate cancer than its current indications and we
remain committed to helping these patients benefit from the treatment in
NOTES TO EDITORS
About high-risk metastatic hormone-naïve
prostate cancer (mHNPC)
Not all prostate cancer is the same. It ranges from cancer confined to
the prostate gland to cancer that has spread outside of the prostate to
the lymph nodes, bones, or other parts of the body. The extent or spread
of prostate cancer determines the stage.9 Hormone-naïve
prostate cancer (HNPC) refers to a stage of the disease when the patient
has not been treated with ADT.10 Patients with newly
diagnosed mHNPC, particularly with high-risk characteristics, have a
poor prognosis. ADT plus docetaxel has shown improved outcomes in mHNPC,
but many patients are not candidates for docetaxel and may benefit from
alternative therapy.11 Also, while the majority of patients
initially start on ADT, it usually becomes less effective over time.6,7,8
About the LATITUDE Trial1
The Phase 3, multinational, multicentre, randomised, double-blind,
placebo-controlled LATITUDE study enrolled 1,199 newly diagnosed
patients with mHNPC and was conducted at 235 sites in 34 countries in
Europe, Asia-Pacific, Latin America, and Canada. A total number of 597
patients were randomised to receive ADT in combination with abiraterone
acetate plus prednisone (n=597), while 602 patients were randomised to
receive ADT and placebo (n=602). Patients included had high-risk mHNPC
documented by positive bone scan or metastatic lesions at the time of
diagnosis on computed tomography (CT) or magnetic resonance imaging
(MRI). Additionally, patients had to have at least two of the three
following high-risk factors associated with poor prognosis:
These results served the basis for Janssen’s Type II variation
application submission to the European Medicines Agency (EMA), seeking
to expand the existing marketing authorisation for abiraterone acetate
plus prednisone or prednisolone to include the treatment of men with
newly-diagnosed metastatic hormone sensitive prostate cancer (mHSPC). If
approved, this will broaden the use of abiraterone acetate plus
prednisone to include an earlier stage of prostate cancer than its
Overall, the safety profile of ADT in combination with abiraterone
acetate plus prednisone was consistent with prior studies in patients
with metastatic castration-resistant prostate cancer (mCRPC). Most
common and anticipated adverse events were elevated incidences of
mineralocorticoid-related hypertension and hypokalemia in the ADT in
combination with abiraterone acetate plus prednisone arm compared with
ADT and placebo. The incidence rate of grade 3 or higher hypertension
(20% vs. 10%) was greater than that observed in prior studies of
abiraterone acetate in mCRPC patients. There were no serious sequelae
from the increased rate of hypertension. The incidence of hypokalemia
was higher than that reported in prior Phase 3 studies of abiraterone
acetate in mCRPC; however, only two patients discontinued treatment due
to hypokalemia and there were no hypokalemia-related deaths.
Mineralocorticoid-associated adverse events were medically manageable,
resulting in the use of the lower 5mg prednisone dose, compared with the
10mg in prior studies.
About abiraterone acetate
Abiraterone acetate plus prednisone / prednisolone is the only approved
therapy in mCRPC that inhibits production of androgens (which fuel
prostate cancer growth) at all three sources that are important in
prostate cancer – the testes, adrenals and the tumour itself.12,13,14
Abiraterone acetate plus prednisone / prednisolone has been approved in
more than 90 countries to date, and has been prescribed to approximately
290,000 men worldwide.15,16
In 2011, abiraterone acetate in combination with prednisone /
prednisolone was approved by the European Commission (EC) for the
treatment of mCRPC in adult men whose disease has progressed on or after
a docetaxel-based chemotherapy regimen.
In December 2012, the EC granted an extension of the indication for
abiraterone acetate permitting its use, in combination with prednisone
or prednisolone, for the treatment of mCRPC, in adult men who are
asymptomatic or mildly symptomatic after failure of androgen deprivation
therapy in whom chemotherapy is not yet clinically indicated.12
The most common adverse reactions seen with abiraterone acetate plus
prednisone / prednisolone include urinary tract infection, hypokalaemia,
hypertension, and peripheral oedema.
For a full list of side effects and for further information on dosage
and administration, contraindications and other precautions when using
abiraterone acetate plus prednisone / prednisolone please refer to the
summary of product characteristics, which is available at: [0.51 to
About the Janssen Pharmaceutical Companies
At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are
working to create a world without disease. Transforming lives by finding
new and better ways to prevent, intercept, treat and cure disease
inspires us. We bring together the best minds and pursue the most
promising science. We are Janssen. We collaborate with the world for the
health of everyone in it. Learn more at www.janssen.com/emea.
Follow us on http://www.twitter.com/janssenEMEA
for our latest news.
Cilag GmbH International; Janssen Biotech, Inc.; and Janssen-Cilag
International NV are part of the Janssen Pharmaceutical Companies of
Johnson & Johnson.
Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined
in the Private Securities Litigation Reform Act of 1995 regarding
product development. The reader is cautioned not to rely on these
forward-looking statements. These statements are based on current
expectations of future events. If underlying assumptions prove
inaccurate or known or unknown risks or uncertainties materialise,
actual results could vary materially from the expectations and
projections of Janssen-Cilag International NV and/or Johnson & Johnson.
Risks and uncertainties include, but are not limited to: challenges and
uncertainties inherent in product research and development, including
the uncertainty of clinical success and of obtaining regulatory
approvals; uncertainty of commercial success; manufacturing difficulties
and delays; competition, including technological advances, new products
and patents attained by competitors; challenges to patents; product
efficacy or safety concerns resulting in product recalls or regulatory
action; changes in behaviour and spending patterns or financial distress
of purchasers of health care products and services; changes to
applicable laws and regulations, including global health care reforms;
and trends toward health care cost containment. A further list and
descriptions of these risks, uncertainties and other factors can be
found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal
year ended January 1, 2017, including in the sections captioned
“Cautionary Note Regarding Forward-Looking Statements” and “Item 1A.
Risk Factors,” and the company’s subsequent filings with the Securities
and Exchange Commission. Copies of these filings are available online at www.sec.gov,
or on request from Johnson & Johnson. None of the Janssen Pharmaceutical
Companies or Johnson & Johnson undertakes to update any forward-looking
statement as a result of new information or future events or
1 Fizazi, K. LATITUDE: A phase III, double-blind,
randomized trial of androgen deprivation therapy with abiraterone
acetate plus prednisone or placebos in newly diagnosed high-risk
metastatic hormone-naive prostate cancer. Abstract LBA3.
Presented at the 2017 American Society of Clinical Oncology (ASCO)
Annual Meeting, 4th June 2017. Available at: http://abstracts.asco.org/199/AbstView_199_181729.html.
Accessed May 2017.
2 International Agency for Research on Cancer (IARC).
GLOBOCAN 2012 Database: Summary Table by Cancer. Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx.
Accessed May 2017.
3 Buzzoni C, et al. Metastatic prostate cancer
incidence and prostate-specific antigen testing: new insights from
the European Randomized Study of Screening for Prostate Cancer.
Eur Urol 2015; 68: 885-890.
4 McPhail S, et al. Stage at diagnosis and early
mortality from cancer in England. B J Cancer 2015; 112: S108-S115.
5 Brasso K, et al. Differences in survival from
prostate cancer in Denmark, Iceland and Sweden. Eur J Cancer 2013;
6 Gillessen S, et al. Management of patients with
advanced prostate cancer: recommendations of the St Gallen
Advanced Prostate Cancer Consensus Conference. Ann Oncol.
7 Cornford P, et al. Guidelines on Prostate Cancer.
Part II: treatment of relapsing, metastatic, and
castration-resistant prostate cancer. Eur Urol. 2017;71:630-642.
8 American Cancer Society. “Treating Prostate Cancer
That Doesn’t Go Away or Comes Back After Treatment.” Available at: https://www.cancer.org/cancer/prostate-cancer/treating/recurrence.html.
Accessed May 2017.
9 My Prostate Cancer Roadmap. Available at: https://www.myprostatecancerroadmap.com/understanding-your-road.
Accessed May 2017.
10 Moul, J.W. Hormone naïve prostate cancer: predicting
and maximizing response intervals. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814946/.
Accessed May 2017.
Ayer Botrel, T. Efficacy and Safety of Combined Androgen
Deprivation Therapy (ADT) and Docetaxel Compared with ADT Alone
for Metastatic Hormone-Naive Prostate Cancer: A Systematic Review
and Meta-Analysis. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911003/.
Accessed May 2017.
12 ZYTIGA® summary of product
characteristics (February 2017). Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002321/WC500112858.pdf.
Accessed May 2017.
13 Hoy, SM. et al. Abiraterone Acetate: A review of its
use in patients with metastatic castration-resistant prostate
cancer drugs. Drugs 2013; 73:2077-2091.
14 Ritch, CR. Cookson, MS. Advances in the management
of castration resistant prostate cancer. BMJ. 2016 Oct
17;355:i4405. Doi: 10.1136/bmj.i4405.
15 Ye,D. A phase 3, double-blind, randomized
placebo-controlled efficacy and safety study of abiraterone
acetate in chemotherapy-naïve patients with mCRPC in China,
Malaysia, Thailand and Russia. Asian Journal of Urology. 2017.Doi.org/10.1016/j.ajur.2017.01.002.
16 Janssen finance reported unit sales (number of
pills) from launch to Dec 2016.