Nexavar in Combination With Chemotherapy Demonstrates Activity in Patients With Advanced Breast Cancer in Two Phase 2 Studies
- Data Presented at 32nd Annual CTRC-AACR San Antonio Breast Cancer Symposium -
WAYNE, N.J. and EMERYVILLE, Calif., Dec. 11
/PRNewswire-FirstCall/ -- Bayer HealthCare Pharmaceuticals and Onyx
Pharmaceuticals, Inc. (NASDAQ:ONXX) today announced results from two
collaborative group-sponsored randomized, double-blind,
placebo-controlled Phase 2 trials were presented at the 32nd Annual
San Antonio Breast Cancer Symposium (SABCS). The first of these
studies evaluated Nexavar® (sorafenib) tablets in combination
with chemotherapy agent capecitabine and the second study evaluated
Nexavar in combination with paclitaxel.
"Onyx and Bayer are encouraged by these results as they suggest
Nexavar may have potential as a combination therapy for advanced
breast cancer patients in both the first and second-line setting,"
said Todd Yancey, M.D., senior vice president of clinical
development at Onyx. "These findings, in particular the
statistically significant results demonstrated with Nexavar in
combination with capecitabine, are the basis for a registrational
Phase 3 program that is expected to begin next year."
Nexavar in Combination with Capecitabine
The randomized, double-blind, placebo-controlled Phase 2 study
evaluated Nexavar in combination with the oral chemotherapeutic
agent, capecitabine, in 229 patients. These patients had locally
advanced or metastatic HER-2 negative breast cancer and had
received no more than one prior chemotherapy in this setting.
Patients receiving capecitabine plus Nexavar had a 74 percent
improvement in progression-free survival as compared to those who
received chemotherapy alone. The increase in median
progression-free survival of capecitabine plus Nexavar versus
capecitabine plus placebo was statistically significant (median 6.4
months vs. 4.1 months, HR=.576, p=0.0006).
In a post-hoc, subgroup analysis of first-line patients, the
combination of capecitabine plus Nexavar significantly extended
progression-free survival to 7.6 months compared to 4.1 months (HR=
0.498, p=0.0022). In a second post-hoc subgroup analysis of
second-line patients, the combination of Nexavar and capecitabine
significantly extended progression-free survival 5.7 months
compared to 4.1 months (HR=0.652, p=0.0339)
The primary endpoint of the study was progression-free survival.
Secondary endpoints included overall survival, time-to-progression,
and safety. Patients were randomized to receive 400 mg of oral
Nexavar or matching placebo twice daily, in addition to 1000 mg/m2
of capecitabine.
Overall, treatment with capecitabine plus Nexavar did not result
in any new side effects.
Common grade 3 treatment-related adverse events included
hand-foot skin reaction (45%), diarrhea (5%), dyspnea (5%),
neutropenia (4%) and mucositis (1%).
Top-line results from this study were previously presented at
the joint 15th European CanCer Organisation (ECCO) and 34th
European Society for Medical Oncology (ESMO) Multidisciplinary
Congress.
Nexavar in Combination with Paclitaxel
The randomized, double-blind, placebo-controlled Phase 2 study
evaluated Nexavar in combination with the chemotherapeutic agent,
paclitaxel, in 237 patients. Patients were randomized to receive
400 mg of oral Nexavar or matching placebo twice daily, in addition
to paclitaxel, given at 90 mg/m2 weekly for three weeks followed by
one week of rest. These patients had locally recurrent or
metastatic HER-2 negative breast cancer and had not received prior
chemotherapy in this setting.
The primary endpoint of the study was progression-free survival
(PFS). The PFS in patients receiving paclitaxel plus Nexavar
compared to patients receiving paclitaxel plus placebo was 6.9
months vs. 5.6 months (HR=0.788, P=0.0857, one-sided).
Secondary endpoints included overall survival,
time-to-progression, and safety. The difference in
time-to-progression of paclitaxel plus Nexavar versus paclitaxel
plus placebo was statistically significant, 8.1 months vs. 5.6
months (HR= 0.674, P=0.017 one-sided).
There were no new toxicities observed with the combination and
adverse events were clinically manageable. Common grade 3
treatment-related adverse events included hand-foot skin reaction
(30%), asthenia (7%), neutropenia (10%) and anemia (10%).
"The results from these two trials fuel our interest in
exploring Nexavar in multiple settings through our comprehensive
clinical program," said Dimitris Voliotis, vice president, Global
Clinical Development Oncology, Bayer HealthCare. "Breast cancer is
the second leading cause of cancer-related death in women, and we
are committed to evaluating Nexavar's role in this often
underserved patient population."
About the Nexavar Clinical Program in Breast Cancer
These two studies are part of a clinical development program
known as TIES (Trials to Investigate the Effects of Sorafenib in
Breast Cancer). Nexavar is being evaluated in collaboration with
investigators and cooperative groups in four large randomized Phase
2 trials for patients with advanced breast cancer and in a variety
of treatment settings. In addition to these two studies, there are
two ongoing randomized Phase 2 studies, including a trial to
evaluate Nexavar plus gemcitabine or capecitabine in the
second-line setting following progression on bevacizumab, and a
trial to evaluate Nexavar plus docetaxel and/or letrozole in the
first-line setting.
About Breast Cancer
Breast cancer was the most commonly diagnosed cancer among women
worldwide in 2007-2008 (approximately 1.3 million cases), and the
second leading cause of cancer-related death among women
(approximately 465,000 deaths). It is the most commonly diagnosed
cancer among women in the United States (1 in 4 cancer diagnoses is
breast cancer). There are approximately 200,000 new cases of breast
cancer in the United States and 430,000 in Europe each year. More
than 40,000 women in the United States and more than 130,000 in
Europe die of breast cancer each year. (i)(ii)(iii)
Nexavar's Differentiated Mechanism
Nexavar, an oral anti-cancer therapy, is currently approved in
more than 80 countries for liver cancer and in more than 90
countries for the treatment of patients with advanced kidney
cancer. Nexavar inhibits both the tumor cell and tumor vasculature.
In preclinical studies, Nexavar has been shown to inhibit members
of two classes of kinases known to be involved in both cell
proliferation (growth) and angiogenesis (blood supply) - two
important processes that enable cancer growth. These kinases
included Raf kinase, VEGFR-1, VEGFR-2, VEGFR-3, PDGFRB, KIT, FLT-3
and RET.
Nexavar is also being evaluated by the companies, international
study groups, government agencies and individual investigators as a
single agent or combination treatment in a wide range of cancers,
including lung, ovarian and colorectal cancer and as an adjuvant
therapy for liver and kidney cancer.
Important Safety Considerations For Patients Taking
Nexavar
Based on the currently approved U.S. package insert for the
treatment of patients with unresectable hepatocellular carcinoma
and advanced kidney cancer, hypertension may occur early in the
course of therapy and blood pressure should be monitored weekly
during the first six weeks of therapy and treated as needed. In HCC
patients, bleeding with a fatal outcome from any site was reported
in 2.4% for Nexavar and 4% in placebo. The incidence of
treatment-emergent cardiac ischemia/infarction was 2.7% for Nexavar
vs. 1.3% for placebo. In RCC patients, incidence of bleeding
regardless of causality was 15% for Nexavar vs. 8% for placebo and
the incidence of treatment-emergent cardiac ischemia/infarction was
2.9% for Nexavar vs. 0.4% for placebo. Most common adverse events
greater than or equal to 20% related to Nexavar for both HCC and
RCC were fatigue, weight loss, rash/desquamation, hand-foot skin
reaction, alopecia, diarrhea, nausea, and abdominal pain. Grade 3/4
adverse events in HCC and RCC patients, respectively, were 45% for
Nexavar vs. 32% for placebo and 38% for Nexavar and 28% for
placebo. Women of child-bearing potential should be advised to
avoid becoming pregnant and advised against breast-feeding. In
cases of any severe or persistent side effects, temporary treatment
interruption, dose modification or permanent discontinuation should
be considered.
For information about Nexavar including U.S. Nexavar prescribing
information, visit www.nexavar.com or call 1.866.NEXAVAR
(1.866.639.2827).
About Bayer HealthCare Pharmaceuticals Inc.
Bayer HealthCare Pharmaceuticals Inc. is the U.S.-based
pharmaceuticals business of Bayer HealthCare LLC, a subsidiary of
Bayer AG. Bayer HealthCare is one of the world's leading,
innovative companies in the healthcare and medical products
industry, and combines the activities of the Animal Health,
Consumer Care, Diabetes Care, and Pharmaceuticals divisions. Bayer
HealthCare Pharmaceuticals comprises the following business units:
Women's Healthcare, Diagnostic Imaging, General Medicine, which
includes Cardiology and Primary Care and Specialty Medicine, which
includes Hematology, Oncology and Multiple Sclerosis. The company's
aim is to discover and manufacture products that will improve human
health worldwide by diagnosing, preventing and treating
diseases.
About Onyx Pharmaceuticals, Inc.
Onyx Pharmaceuticals, Inc. is a biopharmaceutical company
committed to improving the lives of people with cancer. The
company, in collaboration with Bayer HealthCare Pharmaceuticals,
Inc., is developing and marketing Nexavar® (sorafenib) tablets,
a small molecule drug that is currently approved for the treatment
of liver cancer and advanced kidney cancer. Additionally, Nexavar
is being investigated in several ongoing trials in a variety of
tumor types. Beyond Nexavar, Onyx has established a development
pipeline of anticancer compounds at various stages of clinical
testing, including carfilzomib, a next-generation proteasome
inhibitor, that is currently being evaluated in multiple clinical
trials for the treatment of patients with relapsed or
relapsed/refractory multiple myeloma and solid tumors. ONX 0801, a
targeted alpha-folate inhibitor, is currently in Phase 1 testing.
For more information about Onyx, visit the company's website at
www.onyx-pharm.com.
Forward Looking Statements
This news release may contain forward-looking statements based
on current assumptions and forecasts made by Bayer Group or
subgroup management. Various known and unknown risks, uncertainties
and other factors could lead to material differences between the
actual future results, financial situation, development or
performance of the company and the estimates given here. These
factors include those discussed in Bayer's public reports which are
available on the Bayer Web site at www.bayer.com. The company
assumes no liability whatsoever to update these forward-looking
statements or to conform them to future events or
developments.
This news release also contains "forward-looking statements" of
Onyx within the meaning of the federal securities laws. These
forward-looking statements include without limitation, statements
regarding timing, progress and results of the clinical development,
safety, regulatory processes, commercialization efforts or
commercial potential of Nexavar. These statements are subject to
risks and uncertainties that could cause actual results and events
to differ materially from those anticipated. Reference should be
made to Onyx's Annual Report on Form 10-K for the year ended
December 31, 2008, filed with the Securities and Exchange
Commission under the heading "Risk Factors" and Onyx's Quarterly
Reports on Form 10-Q for a more detailed description of such
factors. Readers are cautioned not to place undue reliance on these
forward-looking statements that speak only as of the date of this
release. Onyx undertakes no obligation to update publicly any
forward-looking statements to reflect new information, events, or
circumstances after the date of this release except as required by
law.
Nexavar® (sorafenib) tablets is a registered trademark of
Bayer HealthCare Pharmaceuticals, Inc.
(i) American Cancer Society, 2007 Global Cancer Facts and Figures Report (ii) American Cancer Society, 2009 Global Cancer Facts and Figures Report
(iii) Estimates of the cancer incidence and mortality in Europe
in 2006, Annals of Oncology, 2007 Mar;18(3):581-92
Source: Onyx Pharmaceuticals, Inc.; Bayer HealthCare Pharmaceuticals Inc.
CONTACT: Media, David Freundel of Bayer HealthCare
Pharmaceuticals,
+1-973-866-6082; or Lori Murray of Onyx Pharmaceuticals,
Inc.,
+1-510-590-0800, or Investors, Julie Wood of Onyx Pharmaceuticals,
Inc.,
+1-510-597-6505
Web Site: http://www.onyx-pharm.com/
Posted: December 2009
