To determine the therapeutic outcomes and safety of adjuvant therapy in
the setting, and eventually, a total of 79 GIST patients fulfilling the
inclusion criteria were included in this study (Figure 1). As shown in
Figure 2, distribution of steady-state imatinib Cmin of
postoperative patients with following imatinib adjuvant therapy at least
day 29. Of these patients treated with imatinib 200 mg/d (n=8), 300 mg/d
(n=33), 400 mg/d (n=37) and 600 mg/d (n=1), the mean±standard deviation
(SD) imatinib Cmin was 704±299ng/mL, 1153±473.3ng/mL,
1246±491.3ng/mL, and 1621ng/mL, respectively. Furthermore, these
patients were divided into four groups four groups based on the levels
of imatinib Cmin. The Q1 (335 to 807 ng/mL; n=20), Q2-Q3
(807 to 1347 ng/mL; n=40), and Q4 (1347 to 2919 ng/mL; n =20). The 8
patients in the 200-mg dose group, five were in Q1, three were in Q2-Q3;
for the 33 patients in the 300-mg dose group, 12 patients were in
quartile 1 (Q1), 17 were in Q2-Q3, and seven were in Q4; for the 37
patients in the 400-mg dose group, six were in Q1, 19 were in Q2-Q3, and
12 were in Q4. It is noteworthy that the proportion of patients reaching
the predefined target Cmin (1100ng/mL) was comparable
between both different dose groups, with 54.1% (20/37) of 400-mg dose
group and 48.5% (16/33) of 300-mg dose group reaching the target (P =
0.82). Furthermore, when the predefined target imatinib
Cmin was defined as 760ng/mL, no significant difference
was observed between the above-mentioned two groups (55.9% (33/37) vs.
44.7% (26/33), P=0.33). In addition, the steady-state imatinib
Cmin of 200-mg/day group was significantly lower than
groups of 300- (P=0.036) and 400-mg/day (P=0.013), no significant
difference in the Cmin of 300- and 400 -mg/day group
(P=0.427) (Fig 3A). Additionally, the higher imatinib
Cmin levels in women were observed in the 300 and 400-mg
daily groups when compared with males (Fig 3B). On the other hand, we
excluded the patients with 200mg/d and 600mg/d because of the limited
patients in this study, and eventually, 79 patients were identified for
further analysis. The baseline clinical characteristics of the
aforementioned patients were shown in Table 1.
With regard to the adverse drug reactions (ADRs), as shown in Table 2,
the most common mild adverse reactions were periorbital edema (71.4%),
followed by muscle cramps (59.5%), nausea and vomiting diarrhea
(53.2%), fatigue (35.4%), and et al. Generally, imatinib was well
tolerated, while mild-to-moderate ADRs (grade 1 and 2) were found in
these patients.
The median follow-up for the entire cohort was 51.1 months
(interquartile range (IQR), 33.4 to 65.0 months). A comparison of
prognostic outcomes in the PTW-adjusted cohort showed no significant
difference in RFS between the 300-mg and 400-mg daily groups (Figure4).
The median RFS in the 400-mg daily group was 130 months (95% CI
130–not reached) versus not reached for those in the 300-mg daily group
(p = 0.47). Additionally, the result of multivariate Cox proportional
hazards regression analysis showed that a dose of 300-mg daily has no
significant impact on RFS (hazard ratio [HR] 3.5; 95% confidence
interval [CI] 0.3-44.1). This is consistent with the result (HR 2.3;
95% CI, 0.2-30.4) after the IPTW-adjusted.