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Home>Breast Cancer> Zometa(R) Improved Bone Mineral Density in Breast Cancer Patients Receiving Adju
Zometa(R) Improved Bone Mineral Density in Breast Cancer Patients Receiving Adju
Zometa(R) (zoledronic acid)
injection, an intravenous bisphosphonate administered to more than one million
patients worldwide, was shown to inhibit aromatase inhibitor-induced bone loss
in postmenopausal women treated with Femara(R) (letrozole tablets) in the
adjuvant breast cancer setting.
Final data of the primary endpoint of 12-month bone mineral density (BMD)
demonstrate a significant increase in BMD for those breast cancer patients
treated with Femara and upfront Zometa compared with those who received Femara
and delayed Zometa. These data were presented at the American Society of
Clinical Oncology (ASCO) annual meeting in Orlando, Florida.
Several studies have shown that women treated with hormonal therapy in the
adjuvant breast cancer setting are at risk of bone loss. New data from the Z-
FAST (Zometa-Femara Adjuvant Synergy Trial) study offer evidence that Zometa
may prevent bone loss in these patients. These data are particularly important
given that aromatase inhibitors are a widely prescribed hormonal therapy for
newly diagnosed breast cancer.
"These are valuable and encouraging data for the medical community and
breast cancer patients," said Adam Brufsky, M.D. Ph.D., co-director, Magee
Women's Hospital/UPCI Comprehensive Breast Cancer Center in Pittsburgh, PA and
assistant professor of Medicine at the University of Pittsburgh, principal
investigator. "It is exciting that Zometa has shown activity against bone loss
in breast cancer patients receiving adjuvant treatment with an aromatase
inhibitor."
Study results
The Z-FAST study showed that at the 12-month follow-up, the group of
patients receiving upfront Zometa had a mean increase of lumbar spine BMD of
1.9% vs. a decrease of 2.4% in the group of patients who received delayed
Zometa (p<0.0001). This represents a 4% relative difference in lumbar spine
BMD in favor of the upfront Zometa group. Total hip BMD was also significantly
higher in the upfront group, compared to the delayed group. Significantly, 8%
of patients in the delayed group had decreases in BMD at the 12-month follow-
up, which required initiation of Zometa.
Zometa is generally well tolerated in nonmetastatic cancer patients, as
supported by several trials in this setting. The following adverse events
occurred in more than 5% of patients in the Z-FAST study: arthralgia (30% in
upfront group, 29% in delayed group); hot flashes (25.3%, 25.7%); fatigue
(17.3%, 15.3%); myalgia (12.7%, 9.7%); bone pain (11.3%, 4%); headache (9%,
7.3%); nausea (8%, 5.7%); pain in extremities (8%, 4.3%); insomnia (7%, 5.3%);
depression (5.7%, 9%); back pain (6%, 5.7%).
The Z-FAST study is part of a wider clinical program that includes the
international sister trial Zo-FAST. Zo-FAST, which will include more than 900
patients in 30 countries outside the U.S., is investigating the same primary
and secondary endpoints and will add to this body of clinical evidence.
"We are committed to developing innovative treatments for patients with
cancer," said Diane Young, M.D., vice president, global head, Clinical
Development, Novartis Oncology. "We are pleased that these data suggest that
Zometa may offer breast cancer patients receiving aromatase inhibitors and
their physicians an important new option in the treatment of bone loss."
Study design
The landmark study, Z-FAST, is a multicenter trial designed to help
address two important and previously unanswered clinical questions facing the
breast cancer community: 1) Does adjuvant treatment of breast cancer with an
aromatase inhibitor cause bone loss? 2) Can potential bone loss be prevented
by including an IV bisphosphonate in the treatment paradigm?
This open-label, randomized, multicenter trial enrolled 602 postmenopausal
women with stage I, II, IIIa, estrogen receptor (ER) and/or progesterone
receptor (PR) positive breast cancer who have undergone complete tumor
resection, and have no clinical or radiological evidence of recurrent or
metastatic disease.
Patients will remain in the study and be treated for a maximum of five
years, or until disease progression, with Femara as their adjuvant therapy
beginning day one. Patients were randomized to one of two Zometa treatment
arms, receiving either an upfront 4 mg, 15-minute infusion of Zometa every six
months beginning on day one, or a delayed start 4 mg, 15-minute infusion of
Zometa every six months. The delayed start group received Zometa when
researchers detected a post-baseline bone mineral density T score below -2.0
SD (standard deviation) or after a bone complication has occurred. Patients
will be followed for bone complications including fractures.
About Zometa
An intravenous bisphosphonate, Zometa is the first therapy of its kind to
demonstrate efficacy in reducing or delaying bone complications across a broad
range of tumor types such as breast, prostate, lung and renal cell cancers in
patients with metastatic disease. Prior to Zometa, intravenous
bisphosphonates had only been indicated for use in multiple myeloma and breast
cancer patients with bone metastasis. Zometa offers patients, nurses and
clinicians a convenient 4 mg, 15-minute infusion.
Zometa was granted marketing authorization by the FDA in February 2002 for
the treatment of bone complications in patients with advanced malignancies
involving bone. This indication was based on data from three large pivotal
trials of more than 3,000 patients that evaluated the drug for a treatment
period of approximately one year.
Zometa is indicated for the treatment of patients with multiple myeloma
and patients with documented bone metastases from solid tumors, in conjunction
with standard antineoplastic therapy. In prostate cancer, patients should
have progressed after treatment with at least one hormonal therapy. The solid
tumors studied included, among others, prostate, breast, lung, renal and
colon. Zometa also is indicated for the treatment of hypercalcemia of
malignancy (HCM), the most common life-threatening metabolic complication of
cancer.
About Femara
Femara is a leading once-a-day oral aromatase inhibitor currently
available in more than 90 countries worldwide. Femara is approved for extended
adjuvant treatment of early breast cancer in postmenopausal women who have
completed standard adjuvant tamoxifen therapy in 57 countries worldwide, now
including member countries of the EU as well as the United States. In
addition, it is indicated for first-line treatment of postmenopausal women
with hormone receptor-positive or hormone receptor-unknown locally advanced or
metastatic breast cancer and for the treatment of advanced breast cancer in
postmenopausal women with disease progression following antiestrogen therapy.
Not all indications are available in every country.
Femara safety information
You should not take Femara if you are pregnant as it may cause fetal harm.
You must be postmenopausal to take Femara.
Commonly reported side effects are generally mild to moderate. Those seen
more often with Femara versus placebo were hot flashes (50% vs. 43%), joint
pain (22% vs. 18%) and muscle pain (7% vs. 5%). Other side effects, which were
comparable to placebo, include fatigue (34% vs. 32%), swelling due to fluid
retention (18% vs. 16%), headache (20% vs. 20%), increase in sweating (24% vs.
22%) and increase in cholesterol (16% vs. 16%).
Longer follow up is needed to determine the risk of fracture associated
with long-term use of Femara. The percentage of patients on Femara versus
placebo reporting a fracture was 5.9% vs. 5.5%. The percentage of patients
reporting osteoporosis was 6.9% vs. 5.5%. Bisphosphonates, drugs that increase
bone strength, were given to 21.1% of Femara patients and 18.7% of placebo
patients.
Zometa safety information
In clinical studies, the safety profile with Zometa was similar to that of
pamidronate or placebo. Zometa has been associated with reports of renal
insufficiency. Patients should have serum creatinine assessed prior to
receiving each dose of Zometa. Caution is advised when Zometa is used in
aspirin sensitive patients, or with aminoglycosides, loop diuretics, and other
potentially nephrotoxic drugs. 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.
In clinical trials in patients with bone metastases and hypercalcemia of
malignancy (HCM), Zometa had a safety profile similar to other intravenous
bisphosphonates. 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 as to whether discontinuation of bisphosphonate therapy reduces
the risk of ONJ in patients requiring dental procedures.
The foregoing release contains forward-looking statements that can be
identified by terminology such as "new data," "was shown," "may prevent,"
"encouraging data," "has shown activity," "potential," "suggest," "may offer"
or similar expressions, or by express or implied discussions regarding
potential future sales of Femara and/or Zometa. Such forward-looking
statements involve known and unknown risks, uncertainties and other factors
that may cause actual results with Femara and/or Zometa to be materially
different from any future results, performance or achievements expressed or
implied by such statements. There can be no guarantee that Femara and/or
Zometa will reach any particular sales levels. In particular, management's
expectations regarding commercialization of Femara and/or Zometa could be
affected by, among other things, additional analysis of Femara and/or Zometa
clinical data; new clinical data; unexpected clinical trial results;
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; increased
government, industry, and general public pricing pressures; and other risks
and factors referred to in the Company's current Form 20-F on file with the
U.S. 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 Pharmaceuticals Corporation researches, develops, manufacturers
and markets leading innovative prescription drugs used to treat a number of
diseases and conditions, including central nervous system disorders, organ
transplantation, cardiovascular diseases, dermatological diseases, respiratory
disorders, cancer and arthritis. The company's mission is to improve people's
lives by pioneering novel healthcare solutions.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation
is an affiliate of Novartis AG (NYSE: NVS) -- a world leader in
pharmaceuticals and consumer health. In 2004, the Group's businesses achieved
sales of USD 28.2 billion and pro forma net income of USD 5.6 billion. The
Group invested approximately USD 4.2 billion in RandD. Headquartered in Basel,
Switzerland, Novartis Group companies employ approximately 81,400 people and
operate in over 140 countries around the world. For further information please
consult http://www.novartis.com.
Contacts
Geoff Cook
Novartis Pharma Communications
1 862 778 5587 (direct)
1 973 652 7927 (mobile)
Geoffrey.Cook@novartis.com
John Gilardi
Novartis Global Media Relations
41 61 324 3018 (direct)
41 79 596 1408 (mobile)
John.Gilardi@novartis.com
Novartis Pharmaceuticals Corporation
http://www.novartis.com
 
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