. The ages of these patients ranged from 18 to 91 years. Patients were included who had a histological diagnosis of primary GIST expressing Kit protein by immunochemistry and a tumour size ≥ 3 cm in maximum dimension, with complete gross resection of primary GIST within 14-70 days prior to registration. After resection of primary GIST, patients were randomised to one 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 713 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 8. No benefit was observed in the low and very low risk groups. No overall survival benefit has been observed.
Table 8 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
A second multicentre, open label phase III study (SSG XVIII/AIO) compared 400 mg/day Glivec 12 months treatment vs. 36 months treatment in patients after surgical resection of GIST and one of the following: tumour diameter > 5 cm and mitotic count > 5/50 high power fields (HPF); or tumour diameter > 10 cm and any mitotic count or tumour of any size with mitotic count > 10/50 HPF or tumours ruptured into the peritoneal cavity. There were a total of 397 patients consented and randomised to the study (199 patie |
