U.S. Residents
GIST Frequently Asked Questions
General GIST FAQs
1.1 How common is GIST (gastrointestinal stromal
tumour)?
1.2 Are GISTs benign or malignant?
1.3 Glivec® was approved on phase 2 data in 2002. Are more current data available?
GIST Diagnosis and Treatment Information
2.1 Can Glivec be used to treat patients with malignant, yet localised, disease?
2.2 Does surgical resection eliminate GIST?
2.3 How critical is it to test for KIT in diagnosis of GIST?
2.4 When should molecular mutation testing be performed for GIST?
2.5 I have heard about positron-emission tomography (PET) scanning to monitor the effectiveness of therapy for GIST but do not have access to a PET-scanning facility. Does that mean I cannot prescribe Glivec?
2.6 Does Glivec impact survival in GIST, or is it simply palliative treatment?
2.7 Are adverse events seen with Glivec in patients with GIST similar to those seen in patients with chronic myeloid leukaemia (CML)?
Response to Glivec
3.1 How quickly do patients with GIST respond to Glivec?
3.2 Can I increase the dose for patients who don't respond at the starting dose (ie, 16% of patients)? How long should I wait before doing so?
3.3 Are responses to Glivec durable in patients with GIST?
3.4 Are there data comparing Glivec with surgery (resection) or chemotherapy for the treatment of GIST?
3.5 Does Glivec work in other solid tumours?
3.6 Should I start my patient on 400 mg/d or 600 mg/d?
3.7 What is the optimal length of time to treat my patients with Glivec after achieving a response?
Answers
General
1.1 How common is GIST (gastrointestinal stromal tumour)?
Historically, GIST was underdiagnosed, often mistaken for other soft tissue sarcomas due to a lack of diagnostic markers. Recent findings indicate the incidence of GIST is more common than once believed, with an incidence of 10-20 million persons per year2.
The expression of KIT (CD117) tyrosine kinase is now recognised as a primary diagnostic marker for GIST, making the disease easily distinguishable from other sarcomas.
It is important to perform a diagnostic evaluation for GIST when a patient presents with an unidentified GI mass. Equivocal cases should be referred to an expert centre with experience in diagnosis of GIST.
1.2 Are GISTs benign or malignant?
Many GISTs are overtly malignant (metastatic or invading adjacent organs or structures), while others are of more uncertain malignant potential.
All GISTs have the potential to become malignant.
1.3 Glivec was approved on phase 2 data in 2002. Are more current data available?
Glivec was approved on phase 2 data involving 147 patients whose responses to Glivec therapy were unprecedented in the medical treatment of GIST.
At 52 months of follow-up, results of the pivotal phase 2 B2222 trial have demonstrated that 84% of patients with advanced GIST achieve clinical benefit31,32:
- 2 patients achieved a complete response (1%)
- 98 patients achieved a partial response (67%)
- 23 patients achieved stable disease (16%)
Diagnosis and Treatment
2.1 Can Glivec be used to treat patients with malignant, yet localised, disease?
If GIST is localised, surgery should be considered first.
If a patient has unresectable localised GIST, Glivec therapy is the standard of care6.
Glivec is indicated for the treatment of adult patients with KIT (CD117)-positive unresectable and/or metastatic malignant GIST.
2.2 Does surgical resection eliminate GIST?
GISTs have a high risk of metastatic relapse after initial surgery for localised disease6.
It is critical to maintain long-term follow-up with patients.
Ongoing Management
The use of Glivec as adjuvant or neoadjuvant therapy is being examined in clinical trials.
2.3 How critical is it to test for KIT in diagnosis of GIST?
KIT positivity is recognised as a primary diagnostic marker for GIST. In fact, 95% of GIST patients are KIT positive.
KIT has been recognised as a key factor in the pathogenesis of GIST. Equivocal cases should be referred to an expert centre experienced in GIST diagnosis.
2.4 When should molecular mutation testing be performed for GIST?
For the minority of GIST cases that are not CD117 positive, the diagnosis should be referred to a pathologist who is experienced in diagnosing GIST.
Of the 5% of histologically suspected GISTs that are CD117 negative, molecular analysis for KIT and PDGFRA mutations should be considered6. In mutational analysis of the KIT and PDGFRA genes, about 35% of GISTs that stain negative for KIT may harbour mutations in the PDGFRA gene16.
No. PET scanning is not required for diagnosis or for treatment with Glivec.
CT scan is the imaging modality of choice.
PET scanning can be a valuable tool to assess response to Glivec therapy early in the course of therapy and may be useful to differentiate disease progression if CT proves ambiguous.
2.6 Does Glivec have an impact on survival in GIST, or is it simply palliative treatment?
Glivec has shown marked improvement in survival over previous systemic therapies in advanced GIST.
At 52-month follow-up, results of the pivotal phase 2 B2222 trial have demonstrated that 84% of patients with advanced GIST were able to achieve stable disease or better32:
- 2 patients achieved a complete response (1%)
- 98 patients achieved a partial response (67%)
- 23 patients achieved stable disease (16%)
The median overall survival with Glivec is 4.8 years331,32.
Yes. As in CML, Glivec generally has a mild to moderate adverse events profile in patients with GIST. The most commonly reported drug-related adverse events have been mild nausea, vomiting, diarrhoea, abdominal pain, fatigue, myalgia, muscle cramps, and rash35.
Only 4% of patients discontinued treatment due to drug-related adverse events35.
More myelosuppression is seen in patients with CML than in patients with GIST35.
Response
3.1 How quickly do patients with GIST respond to Glivec?
In the phase 2 pivotal trial of Glivec, 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
Some patients may take longer to respond, so it is important to continue Glivec therapy until progression, intolerance, or patient refusal6.
Yes. Based on limited 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 an 800-mg daily dose, a 26% overall clinical benefit was observed, where 6 patients achieved a partial response and 21 patients experienced stabilisation of their disease35.
Some patients may take longer to respond, so it is important to continue Glivec therapy long enough for a response to occur. Time to response (TTR) varies from patient to patient 43.
- Median TTR is 12 weeks
- 75% of patients responded by 23 weeks
- TTR may take up to 171 weeks
3.3 Are responses to Glivec durable in patients with GIST?
Yes, the Kaplan-Meier estimate of median duration of response is over 2 years.
No head-to-head trials have been conducted. Comparative trials may be considered unethical because of low response rates seen with other drug therapies.
Surgery is the primary therapy for resectable GISTs. However, GISTs have a high risk of metastatic relapse after initial surgery for localised disease6.
Chemotherapy is rarely effective, with a maximum of 5% of patients achieving a partial response.
3.5 Does Glivec work in other solid tumours?
Glivec is indicated for the treatment of the following solid tumours35:
- Adult patients with KIT (CD 117)-positive unresectable and/or metastatic malignant gastrointestinal stromal tumours (GIST)
- Adult patients with unresectable dermatofibrosarcoma protuberans (DFSP) and adult patients with recurrent and/or metastatic
DFSP who are not eligible for surgery
Please refer to local prescribing information for specific indications.
Clinical trials are currently underway in numerous disease settings including both haematological and solid tumour malignancies.
3.6 Should I start my patient on 400 mg/d or 600 mg/d?
The recommended dosage for patients with KIT-positive unresectable and/or metastatic GIST is 400 mg/d35.
There were no differences in response rates between 400-mg and 600-mg dose groups in the phase 2 study B2222. The phase 2 study was not powered to show statistical significance in response rates between the 2 doses.
The adverse events profile is similar between 400-mg and 600-mg dose levels.
3.7 What is the optimal length of time to treat my patients with Glivec after achieving a response?
Guidelines recommend continued Glivec therapy until progression, intolerance, or patient refusal for patients with advanced GIST6. Discontinuation of treatment with Glivec after 1 year-even after complete remission-was associated with a high risk of relapse6.