Clinical significance of pathological complete response in patients with metastatic gastrointestinal stromal tumors after imatinib mesylate treatment--lessons learned

Abstract

Aim: Imatinib mesylate (IM) has substantial efficacy in patients with metastatic gastrointestinal stromal tumors (GISTs), and pathological complete response (pCR) following IM treatment has been sporadically reported; however, its clinical significance for GIST needs to be clarified.

Patients and methods: From 2001 to 2010, 26 out of 171 patients with metastatic GIST who received IM with response or stable disease underwent operation. Among them, 12 operations with pCR were compared to 14 operations without pCR regarding clinicopathological features, mutation status, progression-free survival (PFS), and overall survival (OS). Following the operation, each tumor was assessed immunohistologically, and genetic analysis was performed on the tumor tissue.

Results: Twelve out of 26 (46.2%) patients with metastatic GIST who received IM with response or stable disease had pCR. After a median follow-up of 40.8 months, patients with pCR had significantly better PFS and OS than those without pCR [2-year PFS and OS: 82.5% and 100% versus 35.6% and 49.4%, (p=0.014 and p=0.004) respectively]. Predictive factors for pCR were: origin of GIST, response after IM therapy, and duration of IM use before operation. Patients without pCR had a significantly higher frequency of secondary mutation when compared to those with pCR (47.4% versus 0%; p=0.004).

Conclusion: Patients with colorectal GIST receiving IM who responded more quickly to IM treatment prior to surgery had a higher chance of pCR. pCR results in significantly favorable PFS and OS, however, IM cannot be withdrawn. Patients without pCR had a significantly higher frequency of secondary mutation when compared to those with pCR.

Keywords: Pathological complete response; gastrointestinal stromal tumor; imatinib mesylate.