nts on 12-month arm and 198 patients on 36-month arm), median age was 61 years (range 22 to 84 years). The median time of follow-up was 54 months (from date of randomisation to data cut-off), with a total of 83 months between the first patient randomised and the cut-off date.
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.
Thirty-six (36) months of Glivec treatment significantly prolonged RFS compared to 12 months of Glivec treatment (with overall Hazard Ratio (HR) = 0.46 [0.32, 0.65], p<0.0001) (Table 9, Figure 1).
In addition, thirty-six (36) months of Glivec treatment significantly prolonged overall survival (OS) compared to 12 months of Glivec treatment (HR = 0.45 [0.22, 0.89], p=0.0187) (Table 9, Figure 2).
Longer duration of the treatment (> 36 months) may delay the onset of further recurrences; however the impact of this finding on the overall survival remains unknown.
The total number of deaths were 25 for the 12-month treatment arm and 12 for the 36-month treatment arm.
Treatment with imatinib for 36 months was superior to treatment for 12 months in the ITT analysis, i.e. including the entire study population. In a planned subgroup analysis by mutation type, the HR for RFS for 36 months of treatment for patients with mutations of exon 11 was 0.35 [95% CI: 0.22, 0.56]. No conclusions can be drawn for other less common mutation subgroups due to the low number of observed events.
Table 9 12-month and 36-month Glivec treatment (SSGXVIII/AIO Trial)
12-month treatment arm
36-month treatment arm
RFS
%(CI)
%(CI)
12 months
93.7 (89.2-96.4)
95.9 (91.9-97.9)
24 months
75.4 (68.6-81.0)
90.7 (85.6-94.0)
36 months
60.1 (52.5-66.9)
86.6 (80.8-90.8)
48 months
52.3 (44.0-59.8)
78.3 (70.8-84.1)
60 months
47.9 (39.0-56.3)
65.6 (56.1-73.4)
Survival
36 months
94.0 (89.5-96.7)
96.3 (92.4-98.2)
48 months
87.9 (81.1-92.3)
95.6 (91.2-97.8)
60 months
81.7 (73.0-87.8)
92.0 (85.3-95.7)
Figure 1 Kaplan-Meier estimates for primary recurrence-free survival endpoint (ITT population)
Figure 2 Kaplan-Meier estimates for overall survival (ITT population)
There are no controlled trials in paediatric patients with c-Kit positive GIST. Seventeen (17) patients with GIST (with or without Kit and PDGFR mutations) were reported in 7 publications. The age of these patients ranged from 8 to 18 years and imatinib was given in both adjuvant and metastatic settings at doses ranging from 300 to 800 mg daily. The majority of paediatric patients treated for GIST lacked data confirming c-kit or PDGFR mutations which may have led to mixed clinical outcomes.
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 |
