U.S. Residents
Prescribing Glivec®(imatinib)
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Before the molecular era, the outlook for patients with GIST was bleak. Before the availability of Glivec (imatinib), patients with advanced GISTs had no effective treatment options.
Glivec is the first protein-tyrosine kinase inhibitor to reach the clinic and is thus the most established molecularly targeted agent of its class. Glivec represents a breakthrough in systemic therapy of solid tumours, and mirrors the initial success of this drug in the treatment of CML. Among solid tumours, GIST is a particularly suitable target for Glivec because of the near-universal presence of KIT in this tumour type. In clinical trials, Glivec demonstrated efficacy in advanced GIST and has been well tolerated.
Glivec Efficacy
Glivec is the standard of care in advanced GIST with proven efficacy and durability. No other drug for GIST has established as proven and durable a track record of efficacy and safety as Glivec.
Glivec is approved for treatment of adult patients with KIT (CD117)-positive unresectable and/or metastatic malignant GIST. At 52-month follow-up, results of the pivotal phase 2 B2222 trial have demonstrated that 84% of patients with advanced GIST had a best response of stable disease or better32:
- 2 patients achieved a complete response (1%)
- 98 patients achieved a partial response (67%)
- 23 patients achieved stable disease (16%)
Median duration of response is over 2 years.
The median overall survival with Glivec is 4.8 years31,32.
The median time to response in patients with advanced GIST who achieved at least a partial response was 12 weeks32.
Time to response (TTR) varies from patient to patient43.
- Median TTR is 12 weeks
- 75% of patients responded by 23 weeks
- TTR may take up to 171 weeks
Duration of survival on Glivec therapy is significantly better than comparative survival estimates based on historical data using conventional chemotherapy before the availability of Glivec (see Figure below)44.
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Dosage Information for Glivec
Glivec is supplied as 100-mg and 400-mg film-coated tablets. The recommended starting doses for adult patients in whom Glivec therapy is indicated is 400 mg/d for patients with KIT-positive unresectable and/or metastatic malignant GIST35.
Based on data from phase 2 clinical studies, a dose increase from 400 mg/d to 600 mg/d or 800 mg/d may be considered for patients progressing at lower doses35. In 2 clinical studies (B2222 and S0033), the daily dose of Glivec was escalated to 800 mg in patients progressing at lower daily doses of 400 mg and 600 mg. From the safety data available, escalating the dose to 800 mg daily in patients progressing at lower doses of 400 mg or 600 mg daily does not seem to affect the safety profile of Glivec. In 103 patients escalated to 800-mg daily dose, a 26% overall clinical benefit was observed, in which 6 patients achieved a partial response and 21 patients experienced stabilisation of their disease35.
Dose reduction or treatment interruption is recommended for severe adverse reactions until the event has resolved. Treatment can later be resumed, depending on the initial severity of the event and as appropriate35.
Please refer to local prescribing information for specific indications.
Safety Information for Glivec
While its efficacy has been outstanding, Glivec has also been well tolerated in patients with GIST. Most undesirable effects are of mild to moderate severity, including GI side effects that may be minimised when the medication is taken with a meal and a large glass of water. The most frequently reported adverse events were mild nausea, vomiting, diarrhoea, abdominal pain, fatigue, myalgia, muscle cramps, and rash-which were easily manageable; superficial oedemas were also a common finding35. Fewer than 5% of patients have experienced grade 3/4 adverse effects (such as skin rashes, liver toxicity, fluid retention syndrome, and haemorrhages) that led to discontinuation of treatment.
Glivec represents a significant medical advance in the treatment of neoplastic disease. As the first and most established molecularly targeted, rationally designed drug therapy for GIST, Glivec establishes a new paradigm for future drug development. The clinical trial data have provided proof of its clinical and survival benefits, and with its specific mechanism of action, Glivec offers an effective and well-tolerated therapeutic option for adult patients with KIT-positive unresectable and/or malignant metastatic GIST.
Read about emerging recommendations for Ongoing Management of CML.
