Study of Novartis drug Zometa for potential new use in early breast cancer did not meet primary endpoint in overall study population
0
Novartis International AG /
Study of Novartis drug Zometa for potential new use in early breast cancer did
not meet primary endpoint in overall study population
Processed and transmitted by Thomson Reuters.
The issuer is solely responsible for the content of this announcement.
* Interim results of AZURE trial report Zometa added to standard adjuvant
therapy did not show disease free survival advantage compared to standard
therapy alone[1]
* In subgroup of women with well-established menopause, an improvement in
disease free survival and overall survival was shown in Zometa arm[1]
* Current applications in the US and EU for adjuvant treatment in early breast
cancer will be withdrawn; Novartis to evaluate future plans based on these
new data
* Study results do not impact the current indications for Zometa in preventing
SREs in patients with advanced cancers involving bone and multiple myeloma
and treating HCM
Basel, December 9, 2010 - Results from the second interim analysis of the Phase
III AZURE (Adjuvant Zoledronic acid to redUce REcurrence) trial show that
Zometa(®) (zoledronic acid) did not demonstrate a disease-free survival (DFS)
advantage when added to standard adjuvant (post-surgery) chemotherapy and/or
hormonal therapy in pre- and postmenopausal women with early breast cancer. In a
preplanned analysis based on menopausal status, a benefit in disease free
survival and overall survival was seen in women with well-established menopause
in the Zometa arm[1].
The AZURE trial was conducted to determine if Zometa as adjuvant therapy had a
benefit in preventing recurrences in premenopausal and postmenopausal women with
early breast cancer. The results were presented today at the 33(rd) Annual CTRC-
AACR San Antonio Breast Cancer Symposium in San Antonio, Texas, US[1].
Zometa is currently approved for the reduction or delay of bone complications
(skeletal-related events, or SREs) across a broad range of metastatic cancers
(breast, prostate, lung and other solid tumors) involving bone and multiple
myeloma, as well as for the treatment of hypercalcemia of malignancy (HCM) and
is the most widely used bisphosphonate in the oncology setting.
"These trial results do not impact the current usage of Zometa, which continues
to be a critical treatment for many patients with a broad range of metastatic
cancers and multiple myeloma, " said Hervé Hoppenot, President, Novartis
Oncology. "Although we did not see an overall disease free survival advantage
for early breast cancer patients receiving Zometa in the adjuvant setting, we´re
encouraged that a subset of postmenopausal patients in the trial experienced an
improvement."
The potential anticancer benefit of Zometa was previously observed in a large,
randomized, Phase III study from the Austrian Breast & Colorectal Cancer Study
Group (ABCSG-12 study), which included more than 1,800 premenopausal women with
hormone receptor-positive (HR+) early-stage breast cancer who, following
curative surgery and hormone therapy, including goserelin treatment to suppress
ovarian function and induce menopause, were treated with or without Zometa for
three years[2]. The trial showed that the addition of three years of Zometa
therapy to hormonal therapy following surgery improved disease-free survival by
32% (hazard ratio=0.68 [95% confidence interval 0.51-0.91], P=0.009)[3].
Last year, Novartis filed supplemental marketing authorization applications for
the adjuvant treatment of premenopausal women with HR+ early breast cancer in
conjunction with hormonal therapy in the US and European Union (EU) based on the
results of ABSCG-12. Novartis is currently reviewing the data from the AZURE
trial results, which were expected to be added to the submission. In the
meantime, Novartis will withdraw the current marketing applications and discuss
next steps with health authorities.
Zometa is approved in more than 100 countries for the reduction or delay of bone
complications in multiple myeloma and across a broad range of metastatic cancers
(breast, prostate, lung and other solid tumors) involving bone, as well as for
the treatment of hypercalcemia of malignancy. It is the most widely used
bisphosphonate in the oncology setting and has been used to treat more than 3.9
million patients worldwide.
AZURE study details
AZURE is a randomized, open-label, multicenter, parallel group trial that
enrolled 3,360 women from 174 centers in seven countries[4], [1]. The study is
run by the National Cancer Research Network in the United Kingdom with input
from an international collaborative group[4]. Patients participate in a five-
year treatment phase and a subsequent five-year follow-up phase[4]. A small
subset of patients also received neo-adjuvant (pre-surgery) therapy[4].
The primary endpoint of DFS was to be determined after 940 disease events[4].
The data presented at SABCS are from a second interim analysis performed when at
least 75% (752) of the final events had occurred[1]. Secondary endpoints
included invasive DFS, overall survival, bone metastasis free survival safety,
and other translational endpoints[4]. After a median follow up of 59 months
(interquartile range 53-61), the hazard ratio (HR) for DFS in Zometa-treated
(n=1681) compared to control patients (n=1678) was 0.98 (95% confidence interval
[CI] [0.85-1.13], P=0.79), thus there was no clinically significant benefit
between the treatment groups[1]. The trend toward improved overall survival in
patients on the Zometa arm was not statistically significant (HR=0.85 [95% CI
0.72-1.01], P=0.0726)[1].
In a preplanned analysis of women based on menopausal status, a benefit of
disease free survival and overall survival was seen in women with well-
established menopause in the Zometa arm[1]. An adjusted analysis for imbalances
in prognostic factors (estrogen receptor, lymph node status and tumor stage)
showed this benefit was statistically significant (29% improvement in overall
survival (HR=0.71 [95% CI 0.54-0.94]; P=0.017)[1]. No benefit was seen in
premenopausal women[1].
The tolerability profile of Zometa is well-established and results from this
study were found to be consistent with the known profile[1]. Generally, serious
adverse events (SAE) were similar in both treatment arms[1]. There were 17 cases
of osteonecrosis of the jaw confirmed in the Zometa arm[1]. This represents a
rate of 1.16%, which is consistent with what has been seen in other well
controlled trials[6].
About ZOMETA
Zometa is indicated for the prevention of skeletal related events (pathological
fractures, spinal compression, radiation or surgery to bone, or tumor-induced
hypercalcemia) in patients with multiple myeloma and advanced malignancies
involving bone. An intravenous bisphosphonate, Zometa is the only approved
therapy to demonstrate efficacy in reducing or delaying bone complications in
multiple myeloma and across a broad range of malignancies such as breast,
prostate, lung and renal cell cancers in patients with metastatic disease when
administered monthly. Zometa offers patients, nurses and clinicians a 4 mg, 15-
minute infusion.
Important Safety Information
Zometa has been associated with reports of renal insufficiency. Patients should
be adequately rehydrated and have their serum creatinine assessed prior to
receiving each dose of Zometa. Due to the risk of clinically significant
deterioration in renal function, single doses of Zometa should not exceed 4 mg
and the duration of infusion should be no less than 15 minutes in 100 ml of
dilutent. The risk of renal adverse events may be greater in patients with renal
insufficiency. Zometa is not recommended for treatment of patients with severe
renal impairment. Severe and occasionally incapacitating bone, joint, and/or
muscle pain has been reported in patients taking bisphosphonates including
Zometa. Caution is advised when Zometa is used in aspirin-sensitive patients, or
with aminoglycosides, loop diuretics and other potentially nephrotoxic drugs.
Zometa contains the same active ingredient (zoledronic acid) as found in
Aclasta. Patients being treated with Zometa should not be treated with Aclasta
concomitantly. Zometa should not be used in patients who are pregnant, or plan
to become pregnant, or who are breast-feeding.
In clinical trials, the most commonly reported adverse events included flu-like
syndrome (fever, arthralgias, myalgias, skeletal pain), fatigue,
gastrointestinal reactions, anemia, weakness, cough, dyspnea and edema. Zometa
should not be used during pregnancy. Zometa is contraindicated in patients with
clinically significant hypersensitivity to zoledronic acid or other
bisphosphonates, or any of the excipients in the formulation of Zometa.
Osteonecrosis of the Jaw (ONJ): ONJ has been reported in patients with cancer
receiving treatment including bisphosphonates, chemotherapy, and/or
corticosteroids. The majority of reported cases have been associated with dental
procedures such as tooth extraction. A dental examination with appropriate
preventive dentistry should be considered prior to treatment with
bisphosphonates in patients with concomitant risk factors. While on treatment,
these patients should avoid invasive dental procedures if possible. No data are
available to suggest whether discontinuation of bisphosphonate therapy reduces
the risk of ONJ in patients requiring dental procedures. A causal relationship
between bisphosphonate use and ONJ has not been established.
Please see full Prescribing Information.
Disclaimer
The foregoing release contains forward-looking statements that can be identified
by terminology such as "potential, " "will, " "to evaluate, " "encouraged, "
"expected, " "may, " or similar expressions, or by express or implied discussions
regarding potential new indications or labeling for Zometa or regarding
potential future revenues from Zometa. You should not place undue reliance on
these statements. Such forward-looking statements reflect the current views of
management regarding future events, and involve known and unknown risks,
uncertainties and other factors that may cause actual results with Zometa to be
materially different from any future results, performance or achievements
expressed or implied by such statements. There can be no guarantee that Zometa
will be submitted or approved for any additional indications or labeling in any
market. Nor can there be any guarantee that Zometa will achieve any particular
levels of revenue in the future. In particular, management´s expectations
regarding Zometa could be affected by, among other things, unexpected clinical
trial results, including unexpected new clinical data and unexpected additional
analysis of existing clinical data; unexpected regulatory actions or delays or
government regulation generally; the company´s ability to obtain or maintain
patent or other proprietary intellectual property protection; competition in
general; government, industry and general public pricing pressures; the impact
that the foregoing factors could have on the values attributed to the Novartis
Group´s assets and liabilities as recorded in the Group´s consolidated balance
sheet, and other risks and factors referred to in Novartis AG´s current Form 20-
F on file with the US Securities and Exchange Commission. Should one or more of
these risks or uncertainties materialize, or should underlying assumptions prove
incorrect, actual results may vary materially from those anticipated, believed,
estimated or expected. Novartis is providing the information in this press
release as of this date and does not undertake any obligation to update any
forward-looking statements contained in this press release as a result of new
information, future events or otherwise.
About Novartis
Novartis provides healthcare solutions that address the evolving needs of
patients and societies. Focused solely on healthcare, Novartis offers a
diversified portfolio to best meet these needs: innovative medicines, cost-
saving generic pharmaceuticals, preventive vaccines, diagnostic tools and
consumer health products. Novartis is the only company with leading positions in
these areas. In 2009, the Group´s continuing operations achieved net sales of
USD 44.3 billion, while approximately USD 7.5 billion was invested in R&D
activities throughout the Group. Headquartered in Basel, Switzerland, Novartis
Group companies employ approximately 102,000 full-time-equivalent associates and
operate in more than 140 countries around the world. For more information,
please visithttp://www.novartis.com.
References
[1] Coleman, R. et al. Adjuvant treatment with Zoledronic acid in stage II/III
breast cancer. The AZURE Trial (BIG 01/04). 33(rd) Annual San Antonio Breast
Cancer Symposium. Presentation # S4-5. December 10, 2010.
[2] Gnant, M et al. Endocrine Therapy plus Zoledronic Acid in Premenopausal
Breast Cancer. N Engl J Med. 2009;360:679-91.
[3] Gnant, M et al. Mature results from ABCSG-12: Adjuvant ovarian suppression
combined with tamoxifen or anastrozole, alone or in combination with zoledronic
acid, in premenopausal women with endocrine responsive early breast cancer.
American Society of Clinical Oncology (ASCO) Annual Meeting. 2010. Abstract #
533.
[4] Coleman, R. et al. AZURE Trial Protocol version 5.1. 2008: 1-54.
[5] Coleman, R et al. The effects of adding zoledronic acid to neoadjuvant
chemotherapy on tumour response: exploratory evidence for direct anti-tumour
activity in breast cancer. Brit J Can. 2010;102:1099-1105.
[6] DeBoer, R et al. The effect of zoledronic acid on aromatase inhibitor
associated bone loss in postmenopausal women with early breast cancer receiving
adjuvant letrozole: The ZO-FAST study 5-year final follow-up. 33(rd) Annual San
Antonio Breast Cancer Symposium. Abstract #P5-11-01.
# # #
Novartis Media Relations
Central media line : +41 61 324 2200
Eric Althoff Gloria Vanderham
Novartis Global Media Relations Novartis Oncology
+41 61 324 7999 (direct) +1 862 778 4268 (direct)
+41 79 593 4202 (mobile) +1 862 926 8420 (mobile)
eric.althoff@novartis.com Gloria.vanderham@novartis.com
e-mail: media.relations@novartis.com
Media materials can be accessed at:
http://www.novartisoncology.com/media/index.jsp
Novartis Investor Relations
Central phone: +41 61 324 7944
Susanne Schaffert +41 61 324 3769 North America:
Pierre-Michel Bringer +41 61 324 1065 Richard Jarvis +1 212 830 2433
Thomas Hungerbuehler +41 61 324 8425 Jill Pozarek +1 212 830 2445
Isabella Zinck +41 61 324 7188 Edwin Valeriano +1 212 830 2456
e-mail: investor.relations@novartis.com
--- End of Message ---
Novartis International AG
Postfach Basel
WKN: 904278;ISIN: CH0012005267;
Media Release (PDF):
http://hugin.info/134323/R/1471079/407928.pdf
This announcement is distributed by Thomson Reuters on behalf of
Thomson Reuters clients. The owner of this announcement warrants that:
(i) the releases contained herein are protected by copyright and
other applicable laws; and
(ii) they are solely responsible for the content, accuracy and
originality of the information contained therein.
Source: Novartis International AG via Thomson Reuters ONE
[HUG#1471079]
CH0012005267
