1631P - Predictive factors of the efficacy of dose escalation in patients with advanced gastrointestinal stromal tumor (GIST) who progressed on imatinib 400 mg/day

Background

In Asia, the standard dose of imatinib (IM) for advanced GIST is 400 mg/day regardless of genotype. After failure of 400 mg/day IM, dose escalation of IM to 800 mg/day has been recommended to achieve higher IM plasma concentration. However, its clinical benefit is limited. This study evaluated the predictive factors of the efficacy of dose escalation of IM in patients with advanced GIST who progressed on IM 400 mg/day.

Methods

Clinical data including IM plasma trough level (C_min) in 134 patients with advanced GIST who received IM 800 mg/day after failure of IM 400 mg/day was retrospectively reviewed. Patients were classified into two groups by C_min at IM 400 mg/day (C_min400), high (>1,570 ng/mL, n=38) vs. low (<=1,570 ng/mL, n=96), using a receiver operating characteristic curve. Patients who underwent surgical intervention were censored at the time of surgery.

Results

The median age of patients was 59 (31–77) years, and 63.4% were male. Compared with C_min400, C_min at IM 800 mg/day increased after dose escalation (median 2,990 ng/mL vs. 1,235 ng/mL, paired Wilcoxon-test P<0.001). The objective response and disease control rates with IM 800 mg/day were 7.2% and 66.4%, respectively, and both rates in the low C_min400 group were higher than those in the high C_min400 group (10.3% vs. 0%, P=0.042 and 73.6% vs. 51.4%, P=0.016). mPFS with IM 800 mg/day (mPFS₈₀₀) was 5.4 months. Despite no significant difference in mPFS with IM 400 mg/day by C_min400, mPFS₈₀₀ in low C_min400 was significantly longer than that in high C_min400 (7.2 vs. 2.8 months, P<0.001). In the multivariate analysis, low C_min400 and KIT exon 9 mutation were significant favorable factors for mPFS₈₀₀ compared with high C_min400 and other exon genotypes, respectively (hazard ratio 0.36 and 0.49, P<0.001 and P=0.005). Patients with KIT exon 9 mutation and low C_min400 exhibited significantly longer mPFS₈₀₀ than those without (16.7 vs. 4.8 months, P=0.006).

Conclusions

Dose escalation of IM after progression on IM 400 mg/day was more effective in patients who had low C_min400 as well as KIT exon 9 mutation. Along with genotype, C_min400 should be considered in the treatment decision of dose escalation of IM after failure of the standard dose of IM.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Yoon-Koo Kang.

Funding

Has not received any funding.

Disclosure

Y-K. Kang: Advisory/Consultancy: ALX oncology ; Advisory/Consultancy: Zymeworks; Advisory/Consultancy: Amgen; Advisory/Consultancy: Novartis; Advisory/Consultancy: Macrogenics; Advisory/Consultancy: Daehwa; Advisory/Consultancy: Surface Oncolgy; Advisory/Consultancy: BMS. All other authors have declared no conflicts of interest.