Response Rates to Gleevec
Phase II results-responses to Gleevec in 147 patients with advanced GIST1
(reported 8/15/2002)
| Best Response | 400 mg (Number=73) |
600 mg (Number=74) |
Either Dose (Number=147) |
|---|---|---|---|
| Complete response | 0 | 0 | 0 |
| Partial response (ranged from 50% to 96%) | 36 (49.3%) | 43 (58%) | 79 (53.7%) |
| Stable disease (stable or less than 50% shrinkage) | 23 (31.5%) | 18 (24.3%) | 41 (27.9%) |
| Progressive disease (within 1 to 3 months after study entry) | 12 (16.4%) | 8 (10.8%) | 20 (13.6%) |
| Could not be evaluated | 2 (2.7%) | 5 (6.8%) | 7 (4.8%) |
- The median time to an objective response was 13 weeks.
- Of 9 patients who started on 400 mg and who were later given 600 mg because of disease progression, 1 subsequently had a partial response and 2 had stable disease after the crossover to 600 mg per day.
- 9 patients treated with 400 mg per day and 5 patients treated with 600 mg per day died.
- 5 patients in the 400 mg per day group and 8 patients in the 600 mg-group were withdrawn from the study.
- The estimated one year survival for all patients was 88 percent. Median survival has not been reached as of 8/15/2002.
- 81.6% of patients remained on study as with a follow-up of more than 9 months.
- Standard PET (scans) proved to be a sensitive, rapid, and reliable indicator of response or resistance to Gleevec. In all patients with a response, the [18F] fluoro-2-deoxy-D-glucose uptake in the tumor had decreased markedly from base line as early as 24 hours after a single dose of Gleevec. Increases in tumor-related glycolytic activity, activity at new sites, or both were seen in all patients with disease progression. PET results correlated with subsequent evidence of a response or progression on CT or MRI scans.
Phase I Study results: (Efficacy
2 Portion)Note: Although this was a phase I study, we note that it done subsequent to the phase II study. It is our feeling that the data from the two studies are comparative.
An objective response was achieved in 25 of 36 (69%) GIST patients, 19 (53%) of whom had a confirmed partial response. The remaining 6 patients with an objective response had either an unconfirmed partial response or a 20% to 29% tumor regression. Of GIST patients who did not achieve an objective response, 7 (19%) were stable and only 4 (11%) had progressive disease. Responses were generally rapid, occurring within 8 days of treatment initiation, as revealed by 18FDG-PET scans. Tumor-related symptoms were relieved in 24 of 27 (89%) patients treated with Gleevec, often within a week after beginning therapy. Updated data indicate that with a minimum follow-up of 11 months (range 11 to 15 months), 29 patients were still on treatment; 18/36 (50%) have PR and 11/36 (30%) have SD, resulting in clinical benefit in 80% of patients. A sustained response was not seen in any non-GIST patient (ie, with c-Kit–negative STS), which is consistent with the postulated role of c-Kit in the GIST disease process and the mechanism of action of Glivec.
1.Efficacy and Safety of Imatinib Mesylate in Advanced Gastrointestinal Stromal Tumors-George D. Demetri, M.d., Margaret Von Mehren, M.D., Charles D. Blanke, M.D., Annick D. Van Den Abbeele, M.D., Burton Eisenberg, M.D., Peter J. Roberts, M.D., Michael C. Heinrich, M.D., David A. Tuveson, M.D., Ph.D., Samuel Singer, M.D., Milos Janicek, M.D., Ph.D., Jonathan A. Fletcher, M.D., Stuart G. Silverman, M.D., Sandra L. Silberman, M.D., Ph.D., Renaud Capdeville, M.D., Beate Kiese, M.Sc., Bin Peng, M.D., Sasa Dimitrijevic, Ph.D., Brian J. Druker, M.D., Christopher Corless, M.D., Christopher D. M. Fletcher, M.D., and Heikki Joensuu, M.D.
2. van Oosterom AT, Judson I, Verweij J, et al. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study.-Lancet. 2001;358:1421-1423. This information is furnished by Novartis in their "GIST Clinical Monograph" which is intended for international Medical Professionals.
