Evaluation Of The Safety And Efficacy Of An Oral Molecularly-Targeted Therapy, STI-571, In Patients (PTS) With Unresectable Or Metastatic Gastrointestinal Stromal Tumors (GISTS) Expressing C-KIT (CD117)

Diana Stripp, MD

University of Pennsylvania Cancer
Last Modified: May 14, 2001

Presenter: Charles D. Blanke
Affiliation: Oregon Health Sciences University, Portland, OR


  1. GISTs are cancers which arise from intestinal cells in the abdomen and are characterized by expression of the proto-oncogene c-kit.
  2. c-KIT mutation is seen in 56-80% of GISTs
  3. GISTs are unresponsive to standard chemotherapy with median survival of 66 months with resectable disease, 9-12 months for locally advanced disease, 10-20 months for metastatic disease.
  4. GISTs are are also resistent to radiation therapy.
  5. STI-571 is a molecularly targeted therapy that selectively inhibits BCR-ABL, KIT, and PDGFR tyrosine kinases and is highly effective in Chronic Myelogenous Leukemia (CML). Based on its potential for inhibition of critical c-kit function in GISTs, a phase II trial of STI-571 was initiated.

Materials and Methods:

  1. From 7/6/00 - 3/13/01, 148 pts entered in this randomized, phase II, open-labled study.
  2. Eligibility criteria included unresectable/metastatic GIST, immunohistochemical documentation of c-kit expression, measurable disease, performance status (PS) 0-2 (later included PS3 pts), and absence of severe liver disease.
  3. Patients were equally randomized to a 400 or 600 mg daily oral dose
  4. Patients progressing on 400 mg continued at 600 mg.
  5. 145 patients are evaluable for response and toxicity.
  6. Reponse evaluated by PET, dynamic MRI or repeat biopsy.


  1. Medium age = 54 (range 18-83); Previous therapy: 55% systemic treatment, 16% XRT and 94% surgery.
  2. Grade 3/4 toxicities were seen in 21% of pts, consisting mainly of hemorrhage (GI), liver toxicity, neutropenia, infection and edema. No differences in the toxicity profile between the 2 doseage groups.
  3. Response rates: partial response: overall 59% (50% in 400mg group, 68% in 600 mg group), stable disease: overall 26% (27%, 24%), progression: overall 13% (21%, 5%). No pt advanced from 400mg to 600 mg group responded to increase dosage.
  4. Medium follow up is 4 ½ mos.
  5. No pt has progressed after achieving an objective response, and median survival has not been reached.
  6. c-KIT mutations are seen in 86% of pts. Presence of c-KIT mutation has higher chance to response (p=0.0117)

Authors' Conclusions

  1. There is an acceptable toxicity profile with STI571. Higher dose (600mg daily) does not increase toxicity.
  2. Overall response rate of 59% is much greater than with conventional therapy.
  3. Though not statistically significant, there is a trend of higher response rate with the 600mg dose.
  4. Presence of c-KIT mutation is much more common in GISTs than previously reported.

Clinical/Scientific Implications:

  1. Although STI-571 is now FDA approved for the treatment of CML, we should continue to register GIST patients to clinical trials in order for the medical community to continue accrueing data on this novel therapy.
  2. The results from this trial is very encouraging for GISTs which are unresponsive to conventional therapy, but one need to keep in mind that there are moderate side effects (21% Gr 3-4) associated with this treatment
  3. The follow up is short (4 1/2 mos) and the scientific community awaits long term data.

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OncoLink ASCO 2001 coverage is provided by an unrestricted educational grant from Amgen