ne of the two arms: Glivec at 400 mg/day or matching placebo for one year.
The primary endpoint of the study was recurrence-free survival (RFS), defined as the time from date of randomisation to the date of recurrence or death from any cause.
Glivec significantly prolonged RFS, with 75% of patients being recurrence-free at 38 months in the Glivec group vs. 20 months in the placebo group (95% CIs, [30 - non-estimable]; [14 - non-estimable], respectively); (hazard ratio = 0.398 [0.259-0.610], p<0.0001). At one year the overall RFS was significantly better for Glivec (97.7%) vs. placebo (82.3%), (p<0.0001). The risk of recurrence was thus reduced by approximately 89% as compared with placebo (hazard ratio = 0.113 [0.049-0.264]).
The risk of recurrence in patients after surgery of their primary GIST was retrospectively assessed based on the following prognostic factors: tumour size, mitotic index, tumour location. Mitotic index data were available for 556 of the 773 intention-to-treat (ITT) population. The results of subgroup analyses according to the United States National Institutes of Health (NIH) and the Armed Forces Institute of Pathology (AFIP) risk classifications are shown in Table 7. No benefit was observed in the low and very low risk groups. No overall survival benefit has been observed.
Table 7 Summary of Z9001 trial RFS analyses by NIH and AFIP risk classifications
Risk criteria
Risk Level
% of patients
No. of events /
No. of patients
Overall hazard ratio (95%CI)*
RFS rates (%)
12 month
24 month
Glivec vs placebo
Glivec vs placebo
Glivec vs placebo
NIH
Low
29.5
0/86 vs. 2/90
N.E.
100 vs. 98.7
100 vs. 95.5
Intermediate
25.7
4/75 vs. 6/78
0.59 (0.17; 2.10)
100 vs. 94.8
97.8 vs. 89.5
High
44.8
21/140 vs. 51/127
0.29 (0.18; 0.49)
94.8 vs. 64.0
80.7 vs. 46.6
AFIP
Very Low
20.7
0/52 vs. 2/63
N.E.
100 vs. 98.1
100 vs. 93.0
Low
25.0
2/70 vs. 0/69
N.E.
100 vs. 100
97.8 vs. 100
Moderate
24.6
2/70 vs. 11/67
0.16 (0.03; 0.70)
97.9 vs. 90.8
97.9 vs. 73.3
High
29.7
16/84 vs. 39/81
0.27 (0.15; 0.48)
98.7 vs. 56.1
79.9 vs. 41.5
* Full follow-up period; NE – Not estimable
Clinical studies in DFSP
One phase II, open label, multicentre clinical trial (study B2225) was conducted including 12 patients with DFSP treated with Glivec 800 mg daily. The age of the DFSP patients ranged from 23 to 75 years; DFSP was metastatic, locally recurrent following initial resective surgery and not considered amenable to further resective surgery at the time of study entry. The primary evidence of efficacy was based on objective response rates. Out of the 12 patients enrolled, 9 responded, one completely and 8 partially. Three of the partial responders were subsequently rendered disease free by surgery. The median duration of therapy in study B2225 was 6.2 months, with a maximum duration of 24.3 months. A further 6 DFSP patients treated with Glivec were reported in 5 published case reports, their ages ranging from 18 months to 49 years. The adult patients reported in the published literature were treated with e |
