Preoperative imatinib for locally advanced gastrointestinal stromal tumors (GIST): CONVERT trial.

Abstract

130 Background: Primary GISTs are frequently diagnosed as large masses requiring wide resections. Our primary objective is to evaluate response rate of imatinib through RECIST and Choi criteria in these patients. Secondary endpoints were downstaging, resectability, safety and tolerability. Methods: This phase II Brazilian study was conducted in 7 centers between 2008 and 2012. To standardize elegibility, inclusion criteria took into account the primary site, size and multi-visceral resection need per surgeon evaluation. Thirty-nine non-metastatic GIST patients with measurable disease and no previous systemic or local treatment were assigned to daily imatinib 400mg for 16 weeks followed by surgery or until medical decision, progressive disease or toxicity. Imatinib could be continued whether adjuvant or palliative according to risk stratification and residual disease. Clinicaltrials.gov NCT01483014. Results: The objective response rate was 32,1% (IC95% 17,9% - 50,7%) on RECIST and 78,6% (IC95% 60,5% - 89.8%) on Choi. One patient (3,8%) had progressive disease, six patients (20%) had serious adverse events with two (6,7%) deaths, not related to the study drug. Treatment discontinuation due to intolerance was observed in 10% of patients caused by extremities pain, nausea, neutropenia, constipation and thrombocytopenia. Surgery was performed on 23 patients (82.1%), with 83,3% being R0. Median tumor size was 9,4cm (1,2 to 22,0cm) and 72,7% had <5 mitosis/50HPF. Conclusions: Imatinib is active and safe in the preoperative setting. Although Choi criteria evaluates responses earlier, a longer course of imatinib, from 6 to 12 months, should be studied to evaluate if longer courses can increase tumor shrinkage and improve this strategy’s usefulness. Clinical trial information: NCT01483014.