NICE Guidance on Glivec® for GIST

Here is the summary of the guidance issued by the National Institute for Clinical Excellence (NICE) on the use of Glivec (Imatinib is the chemical name for Glivec).

The NICE recommendations are the numbered paragraphs and GIST Cancer UK comments are given as "Translation and Comment" below

1.1 Imatinib treatment at 400 mg/day is recommended as the first-line management of people with KIT (CD117)-positive unresectable and/or KIT (CD117)-positive metastatic gastro-intestinal stromal tumours (GISTs).

Translation and Comment:
"Unresectable" means inoperable, "metastatic" means spreading to other areas of the body. "First line management" means treatment of choice. Obviously if tumours are operable then the first-line management is surgery to get rid of the tumour.

KIT-positive tumours are the most common type of GIST.

1.2 Continuation with imatinib therapy is recommended only if a response to initial treatment (as defined in Section 1.5) is achieved within 12 weeks.

Translation and Comment:
Treatment with Glivec is to be continued only if the GIST "responds" within 12 weeks of starting the drug. This is the most controversial item in the NICE Guidance and is discussed below after paragraph 1.5

1.3 Responders should be assessed at intervals of approximately 12 weeks thereafter. Continuation of treatment in responders to imatinib therapy is recommended at 400 mg/day until the tumour ceases to respond, as defined in Section 1.5.

Translation and Comment:
"Responders" are GIST patients for whom the drug treatment causes shrinkage or disappearance of the tumours or whose tumours stop growing and become stable. Again the recommendation is that the treatment should stop if the tumours start to grow again.

1.4 An increase in the dose of imatinib is not recommended for people receiving imatinib who develop progressive disease after initially responding (see Section 1.5).

Translation and Comment:
If a patient stops responding to the drug; i.e. the tumour(s) start to grow again, increasing the dose of the drug is not recommended. This is a recommendation which is in dispute and contrary to the experience of some patients and some oncologists. Latest evidence from trials of Glivec shows that, in some patients, growth can be stopped by an increased dose. When all these data are published, this recommendation may well be dropped.

1.5 For the purpose of this guidance, response to imatinib treatment should be assessed on the basis of the results of diagnostic imaging to assess size and density of the tumour(s), patients' symptoms and other factors, in accordance with the Southwest Oncology Group (SWOG) criteria detailed in Appendix D. For the purpose of this guidance, response to therapy is defined as the SWOG classifications of complete response , partial response or stable disease.

Translation and Comment:
"Diagnostic Imaging" means (in the UK) X-ray CT scans. Appendix D to the report just gives a technical description of the criteria used. "Complete response" means complete disappearance of the tumours, "partial response" means shrinkage of the tumours and "stable disease" means that the tumours stop growing.

The way in which the tumours respond to Glivec is the all-important matter here. Many patients' tumours show shrinkage well within the 12-week period, while others may take many months to respond. Equally important, CT scans can only measure the size and (less precisely) the density of the tumours. There is a good deal of evidence that some tumours are "killed" from the inside by Glivec without changing size and may well become operable if treated for long enough. These cases would be missed if the 12-week deadline is imposed strictly. A much better way of judging the response to Glivec is by PET scanning which measures how active the tumours are by measuring the cell processes. This type of scan can often show response to Glivec within days of starting taking the drug. Unfortunately this scanning technique is not yet widely available in the UK. However, it is to be hoped that, in allowing "other factors" in the assessment of a patient a more flexible diagnosis can be given based on an oncologist's experience with each patient.

1.6 The use of imatinib should be supervised by cancer specialists with experience in the management of people with unresectable and/or metastatic GISTs.

Comment:
Seems an obvious recommendation

Since the NICE Guidance was published, clinical research has moved on in various ways, and we are hoping for a review of this Guidance.

(Last updated December 2008)

Posted: 02/12/2010