Glivec (REG) significantly improves progression-free survival for patients with gastrointestinal stromal tumor

Main Category: GastroIntestinal / Gastroenterology
Article Date: 25 Sep 2004 - 12:00 PDT

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Patients in a study taking an 800 mg daily dose of Glivec (imatinib)* for treatment of certain forms of gastrointestinal stromal tumor (GIST) had significantly longer progression-free survival compared to the patients taking the standard 400 mg daily dose, according to results published today in The Lancet.

The results showed that doubling the daily dose of Glivec may improve progression-free survival of patients with KIT (CD117)-positive inoperable and/or metastatic** GIST. At a median follow-up of 760 days, patients receiving 800 mg per day experienced five months longer progression-free survival compared to patients receiving the 400 mg daily dose.

"The introduction of Glivec has dramatically improved the prognosis of patients diagnosed with advanced KIT-positive GIST," said Jaap Verweij, Head of The Division of Experimental Chemotherapy, Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands, the principal investigator and lead author of this publication. "While further research is needed to establish the impact of a higher starting dose on patients' survival, the prolonged progression-free survival seen in this study represents benefit to patients."

The international, randomized, Phase III intergroup study was conducted by the EORTC (European Organization for Research and Treatment of Cancer), ISG (Italian Sarcoma Group) and the AGITG (Australasian Gastrointestinal Trials Group). A total of 946 patients with advanced and/or metastatic KIT-positive GIST received either a 400 or 800 mg dose of Glivec per day (400 mg twice daily). Patients who experienced any disease progression on the 400 mg daily dose were allowed to increase to 800 mg per day to regain control of the disease. At the time of the analysis (May 2004), a total of 412 patients had completed treatment in the trial, which had progression-free survival as the primary endpoint.

Patient treatment with 800 mg of Glivec per day significantly increased progression-free survival compared to treatment with 400 mg per day. Although side effects were more common and more severe with the higher dose, the majority of patients did not require a dose reduction. Treatment in both groups was fairly well-tolerated.

About GIST

GIST is the most frequent form of gastrointestinal cancer, a life-threatening disease highly resistant to traditional treatment with chemotherapy and radiation. Surgery is considered the best way to initially treat GIST. However, many GISTs cannot be surgically removed because they are too large or have already spread to other parts of the body before diagnosis. When surgery is performed, cells from the original GIST may remain behind or the cancer may return in another site within the body. Experts believe that GIST may be more prevalent than previously believed, affecting approximately 15 people per 1 million per year. In the past, GIST was considered to be untreatable if doctors could not remove the tumor by surgery or if it had spread to other parts of the body.

In GIST, a specific mutation causes a cellular enzyme, known as KIT, to be switched "on" all the time. KIT is an enzyme (called a "tyrosine kinase") responsible for sending growth and survival signals inside the cell. If it is "on," the cell stays alive and grows or proliferates. The overactive, uncontrolled mutant KIT enzyme triggers the runaway growth of GIST tumor cells. This insight into the way GISTs develop has already helped to identify new treatments for this sarcoma.

About Glivec

Glivec is indicated in the EU, US and more than 45 other countries worldwide for the treatment of patients with KIT (CD 117)-positive unresectable (inoperable) and/or metastatic malignant GIST. In Japan, Glivec is approved for the treatment of patients with KIT (CD117)-positive GIST.

Glivec is also approved for first-line treatment of adult patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase, in the EU, US and Japan and a number of other countries. It is also approved in some countries (including the EU and Switzerland) for the treatment of certain pediatric patients with CML. In addition, Glivec is approved in over 80 countries for the treatment of adult patients with Ph+ CML in blast crisis, accelerated phase or in chronic phase after failure of interferon-alpha therapy.

Contraindications and adverse events

The most common undesirable effects experienced during Glivec treatment in GIST are: headache, nausea, vomiting, diarrhea, dyspepsia, myalgia, muscle spasm and cramps, joint swelling, dermatitis, eczema, rash, edema, fluid retention, neutropenia, thrombocytopenia or anemia.

In the first-line study (IRIS), the safety profile with Glivec was similar to that of previous Phase II studies in other CML patients. The majority of patients treated with Glivec experienced adverse events at some time. Most events were of mild to moderate grade and treatment was discontinued for adverse events only in 2% of patients in chronic phase, 3% in accelerated phase and 5% in blast crisis. The most common side effects included nausea, superficial edema, muscle cramps, skin rash, vomiting, diarrhea, hemorrhage, fatigue, headache, joint pain, cough, dizziness, dyspepsia and dyspnea, as well as neutropenia and thrombocytopenia.

Glivec is contraindicated in patients with known hypersensitivity to imatinib or any of its excipients. Women of childbearing potential should be advised to avoid becoming pregnant while taking Glivec.

The foregoing release contains forward-looking statements that can be identified by terminology such as "improve," "may", "may prolong," "significantly increased" or similar expressions, or by express or implied discussions regarding potential future revenue from Glivec. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Glivec to be materially different from any future results, performance or achievements expressed or implied by such statements. In particular, management's expectations regarding Glivec could be affected by, among other things, additional analysis of Glivec 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 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.

*In the U.S.: Gleevec® (imatinib mesylate)
**Metastatic patients are patients whose tumors have spread to other parts of the body

About Novartis
Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2003, the Group's businesses achieved sales of USD 24.9 billion and a net income of USD 5.0 billion. The Group invested approximately USD 3.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 80,000 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.

Further information on Novartis Oncology and Glivec can be found at http://www.novartisoncology.com or http://www.glivec.com.

Additional media information can be found at http://www.novartisoncologyvpo.com.

Contacts

Nadine Schecker
Novartis Global Communications
Tel. +41 61 324 2710
Or +41 61 324 2200
nadine.schecker@group.novartis.com

Eric Althoff
Novartis Pharma Communications
Tel. +41 61 324 6392
Or +41 79 593 4202
eric.althoff@pharma.novartis.com

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