Combined Operation Modality vs. Imatinib Mesylate Alone for Patients with Recurrent or Metastatic Gastrointestinal Stromal Tumors: the Randomized COMVIA Trial

Abstract： Objectives:Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. For advanced GIST patients who are responding to imatinib mesylate, the role of surgery has not been formally demonstrated. Therefore, this multicenter, randomized, controlled trial was designed to assess whether surgeries to treat residual disease for patients with recurrent/metastatic GISTs responding to imatinib mesylate (IM) improves progression free survival (PFS) compared with IM treatment alone. Methods: Between 3 and 12 months after starting molecular-targeted therapy with IM for recurrent/metastatic GISTs, eligible patients were randomized to two arms: Arm A (surgery for residual disease) and Arm B (IM treatment alone). In Arm A (19 pts), surgery was performed to remove residual macroscopic lesions as completely as possible, and IM treatment continued after surgery. In Arm B (22 pts), IM was given alone at a dose of 400mg per day until disease progression. The primary endpoint was PFS, measured from the date IM starts. This study is registered in the ChiCTR registry with the ID number ChiCTR-TRC-00000244. Results: This randomized trial was closed early due to poor accrual. Only 41 patients were enrolled as opposed to 210 planned. After a median follow-up of 23 months (ranging from 15-34 months), the 2-year PFS was 88.4% in the surgery arm and 57.7% in the IM-alone arm (P=0.089). A trend towards survival benefit is observed in the surgery arm; however, it did not result in a statistically significant improvement in PFS. The most likely reason was the limited number of eligible patients, which was well below expectation. Conclusions: Surgeries to treat residual disease for patients with recurrent/metastatic GISTs responding to IM showed a trend to prolonging 2-year PFS compared with IM treatment alone, but no statistically significant conclusion is drawn from the study.