Imatinib-associated skin rash is related to treatment outcome in patients with unresectable and/or metastatic gastrointestinal stromal tumor

Background: Imatinib-associated skin rash in gastrointestinal stromal tumor (GIST) patients is one of the most troublesome adverse effects, and can reduce imatinib adherence and persistence. However, the relationship between skin rash and adherence is unknown, and there are few published studies on the clinical outcomes of patients with severe skin rash. Methods: Adult patients (>= 18 years) who were treated with 400 mg/day imatinib for unresectable or metastatic GIST were enrolled in this retrospective study. The skin rash was graded by physicians according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Progression-free survival (PFS) was compared using the Kaplan-Meier method between groups with and without skin rash. The risk factors for GIST progression were investigated by Cox regression analysis. Results: A total of 125 GIST patients were finally included. Among them, 43 (34.4%) patients developed skin rash during imatinib treatment. Serial blood eosinophil levels were associated with skin rash and severity (P<0.001). Patients with skin rash tended to have poorer PFS than patients with no rash (P=0.035). Moreover, patients with rash had a significantly higher prevalence of non-adherence compared with patients without rash [odds ratio (OR): 3.42, 95% confidence interval (CI): 1.36-8.61, P=0.009 for grades 1-2; OR: 6.07, 95% CI: 1.42-26.11, P=0.015 for grades 3-4). Cox regression analysis indicated that the independent risk factors for GIST progression were non-adherence ( OR: 4.20, 95% CI: 1.57-11.25, P=0.004) and medium- and high-risk GIST (OR: 5.38, 95% CI: 1.15-25.09, P=0.032). Conclusions: Non-adherence and medium- and high-risk GIST are independent risk factors for GIST progression. Skin rash can be associated with treatment adherence, which can in turn be associated with poor outcomes of GIST treatment. Measuring the blood eosinophil levels could be helpful in predicting risk of skin rash during imatinib treatment.