Investigators will begin
offering Gleevec(R) (imatinib mesylate) tablets to patients receiving
placebo in a major North American clinical trial after an interim analysis
showed participants with Kit-positive gastrointestinal stromal tumors
treated with Gleevec following surgery were significantly less likely to
experience a return of their cancer compared to those not taking this
innovative therapy.
The interim analysis showed no recurrence of cancer in approximately
97% of patients given Gleevec for a year after surgery to remove tumors,
compared to approximately 83% of those who underwent surgery but received a
placebo. The investigators made these results public because the study had
met its primary endpoint in terms of rate of recurrence-free survival.
The study involving more than 600 patients was sponsored by the
National Cancer Institute (NCI), part of the US National Institutes of
Health (NIH). It was conducted at multiple cancer centers in the US and
Canada, and was led by the American College of Surgeons Oncology Group.
Novartis supplied Gleevec for use in the study, and also provided partial
funding under a Cooperative Research and Development Agreement with NCI to
support the clinical development of Gleevec.
Gleevec has already been confirmed as an effective therapy in its
approved use for patients with advanced metastatic or unresectable
(inoperable) Kit- positive GIST. In a statement issued today by the NIH,
the new findings were heralded as excellent news, with major implications
for patients with primary disease.
"With these new data, we see that Gleevec may help patients with early
GIST," said Diane Young, MD, Head of Global Medical Affairs at Novartis
Oncology. "We will now work with the investigators on a submission to gain
regulatory approval for Gleevec as adjuvant treatment for GIST."
Following the recommendation of a data monitoring committee, the study
will be closed and patients in the study who are currently being treated
with placebo may choose to receive one year of Gleevec.
In the study, patients were randomized to one of two treatment arms.
Neither the patients nor physicians knew which treatment the patients were
receiving. One patient group received Gleevec at a dose of 400 milligrams
per day for one year, while the second group received placebo for one year.
According to the study design, patients who developed a recurrence of their
cancer while on a study therapy were unblinded to their treatment
assignment. Those receiving placebo subsequently received Gleevec, while
those already given Gleevec continued with this therapy but at a higher
dose. Study results will be presented at a forthcoming scientific meeting.
Gastrointestinal stromal tumors (GIST) belong to a group of cancers
known as soft tissue sarcomas that usually arise from the intestinal tract,
with the most common site being the stomach followed by the small
intestine. The incidence of GIST is estimated to be 4,500-6,000 new cases
per year in the US (15-20 cases per million population), of which more than
90% are kit-positive.
Investigators in the NCI study reported that Gleevec therapy was well
tolerated by most patients, with side effects similar to those observed in
other clinical trials with Gleevec. These include nausea, diarrhea and
swelling (edema). Information on more than 600 patients enrolled in the
study was used in the analysis.
About Gleevec
Gleevec(R) (imatinib mesylate) is indicated for the treatment of
patients with Kit (CD117)-positive unresectable and/or metastatic malignant
gastrointestinal stromal tumors (GIST). The effectiveness of Gleevec in
GIST is based on objective response rate. There are no controlled trials
demonstrating a clinical benefit, such as improvement in disease-related
symptoms or increased survival
Important Safety Information(1)
Severe (NCI Grades 3/4) lab abnormalities (400 mg/day; 600 mg/day)-
including neutropenia (10%; 11%), anemia (3%; 9%), thrombocytopenia (0%;
1%), and hepatotoxicity (6%; 8%)-and severe adverse experiences (NCI Grades
3/4), including severe fluid retention (eg, pleural effusion or ascites;
3%; 8%) and superficial edema (6%; 5%), hemorrhage (6%; 11%), abdominal
pain (11%; 4%), nausea (6%; 4%), diarrhea (3%; 7%), and musculoskeletal
pain (6%; 1%) were reported among patients receiving Gleevec
Some patients (5%) were reported to have severe GI bleeds and/or
intratumoral bleeds. GI tumor sites may have been the source of GI bleeds
Patients should be weighed and monitored regularly for signs and
symptoms of edema, which can be serious or life-threatening. There have
also been reports, including fatalities, of cardiac tamponade, cerebral
edema, increased intracranial pressure, papilledema, and gastrointestinal
(GI) perforation
Severe congestive heart failure and left ventricular dysfunction have
occasionally been reported. Most of the patients with reported cardiac
events have had other comorbidities and risk factors, including advanced
age and previous medical history of cardiac disease. Patients with cardiac
disease or risk factors for cardiac failure should be monitored carefully,
and any patient with signs or symptoms consistent with cardiac failure
should be evaluated and treated
Bullous dermatologic reactions (eg, erythema multiforme and Stevens-
Johnson syndrome) have also been reported. In some cases, the reaction
recurred upon rechallenge. Several postmarketing reports describe patients
able to tolerate the reintroduction of Gleevec at a lower dose with or
without concomitant corticosteroids or antihistamines following resolution
or improvement of the bullous reaction
Dose adjustments may be necessary due to hepatotoxicity, other
nonhematologic adverse events, or hematologic adverse events. Therapy with
Gleevec was discontinued for adverse events in 5% of patients at both dose
levels studied
Patients with severe hepatic impairment should be treated at a starting
dose of 300 mg/day and should be closely monitored
Gleevec is metabolized by the CYP3A4 isoenzyme and is an inhibitor of
CYP3A4, CYP2D6, and CYP2C9. Dosage of Gleevec should increase by at least
50%, and clinical response should be carefully monitored, in patients
receiving Gleevec with a potent CYP3A4 inducer such as rifampin or
phenytoin. Examples of commonly used drugs that may significantly interact
with Gleevec include acetaminophen, warfarin, erythromycin, and phenytoin.
(Please see full Prescribing Information for other potential drug
interactions)
For daily dosing of 800 mg and above, dosing should be accomplished
using the 400 mg tablet to reduce exposure to iron
Use of Gleevec tablets is contraindicated in patients with
hypersensitivity to imatinib or to any other component of Gleevec tablets
Women of childbearing potential should be advised to avoid becoming
pregnant while taking Gleevec tablets and should be advised to avoid
breast- feeding while taking Gleevec tablets because of the potential for
serious adverse reactions in nursing infants
Common Side Effects of Gleevec Tablets
The majority of patients who received Gleevec in the GIST study
experienced adverse events at some time. Most adverse events were mild to
moderate in severity. The most frequently reported adverse events (400
mg/day; 600 mg/day) (all Grades) were superficial edema (81%; 77%), nausea
(63%; 74%), muscle cramps (47%; 58%), diarrhea (59%; 70%), fatigue (48%;
53%), abdominal pain (40%; 37%), rash and related terms (38%; 53%),
vomiting (38%; 35%) musculoskeletal pain (37%; 30%), and hemorrhage (26%;
34%)
Supportive care may help management of some mild to moderate adverse
events so that the prescribed dose can be maintained whenever possible.
However, in some cases, either a dose reduction or interruption of
treatment with Gleevec may be necessary
Gleevec tablets should be taken with food and a large glass of water to
minimize GI irritation. Gleevec tablets should not be taken with grapefruit
juice
Disclaimer
The foregoing release contains forward-looking statements that can be
identified by terminology such as "will," "planned," or similar
expressions, or by express or implied discussions regarding potential
future regulatory submissions, new indications or new labeling for Gleevec,
the long-term impact of a patient's use of Gleevec or potential future
sales of Gleevec. Such forward-looking statements involve known and unknown
risks, uncertainties and other factors that may cause actual results to be
materially different from any future results, performance or achievements
expressed or implied by such statements. There can be no guarantee that
additional regulatory submissions will be made in any particular
jurisdictions, or that Gleevec will be approved for any additional
indications or labeling in any market. Nor can there be guarantee regarding
the long-term impact of a patient's use of Gleevec. Neither can there be
any guarantee regarding potential future sales of Gleevec. In particular,
management's expectations regarding Gleevec could be affected by, among
other things, unexpected clinical trial results, including additional
analysis of Gleevec clinical data, and new 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; and other risks and factors
referred to in the Company'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 this information as
of this date and does not undertake any obligation to update any
forward-looking statements contained in this document as a result of new
information, future events or otherwise.
About Novartis
Novartis Pharmaceuticals Corporation researches, develops, manufactures
and markets leading innovative prescription drugs used to treat a number of
diseases and conditions, including those in the cardiovascular, metabolic,
cancer, organ transplantation, central nervous system, dermatological,
gastrointestinal and respiratory areas. 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
offering medicines to protect health, treat disease and improve well-being.
Our goal is to discover, develop and successfully market innovative
products to treat patients, ease suffering and enhance the quality of life.
Novartis is the only company with leadership positions in both patented and
generic pharmaceuticals. We are strengthening our medicine-based portfolio,
which is focused on strategic growth platforms in innovation-driven
pharmaceuticals, high-quality and low-cost generics, human vaccines and
leading self-medication OTC brands. In 2006, the Group's businesses
achieved net sales of USD 37.0 billion and net income of USD 7.2 billion.
Approximately USD 5.4 billion was invested in R&D. Headquartered in Basel,
Switzerland, Novartis Group companies employ approximately 101,000
associates and operate in over 140 countries around the world. For more
information, please visit novartis.
1 Gleevec(R) (imatinib mesylate) tablets prescribing information. East
Hanover, NJ: Novartis Pharmaceuticals Corporation; Nov 2006.
Novartis Pharmaceuticals Corporation
novartis
View drug information on Gleevec; Warfarin Sodium tablets.
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