A long-term analysis of imatinib palliative treatment in gastrointestinal stromal tumors
Authors: I. Domingues, J. Carvalho, E. Pratas, S. Pinheiro, S. Amaral, N. Bonito, E. Jesus, J. Ribeiro, A. Chaves, A. Pais, G. Sousa
Journal: Annals of Oncology (2018)

Introduction: Gastrointestinal stromal tumor (GIST) is the most common sarcoma accounting for 18% of all sarcomas. It can occur anywhere along the gastrointestinal tract, but mostly in the stomach and small bowel. Historically, GISTs are aggressive tumors with poor prognosis. Imatinib is the first line therapy for GIST patients with unresectable, recurrent, or metastatic disease. Methods: We collected to our analysis patients with GIST treated with imatinib between November/2002 and February/2018. Clinical, pathological and molecular characteristics were retrospectively analyzed. The long-term impact of imatinib in palliative setting was evaluated along the past 16 years, in our medical oncology department. Results: Imatinib therapy was made in 42 patients. A total of 37 were included in our analysis, after the exclusion of 5 patients due to loss of follow-up. Palliative treatment with imatinib was performed in 62.2% (n = 23) of these patients. Their median age was 47 years (± 16.9; 25 to 76), 56.5% male patients (n = 13). Gastric GIST represented 47.8%, followed by small bowel (34.8%) and rectum (8.7%). KIT exon 11 mutation was detected in 54.5% of these patients, 9.1% were wild type, the remaining patients had unknown or unevaluated mutation. No survival differences were detected between these groups. They were all treated with imatinib 400mg as frontline therapy. Median time since primary diagnosis until imatinib was 11.7 months. Best treatment response to the frontline imatinib was stable disease in 56.5% (n = 13), partial response in 26.1% (n = 6), complete response in 13.0% (n = 3) of patients. Frontline imatinib median duration was 25.5 months (0.9 to 84.6). Disease progression led to imatinib discontinuation in 83.3% (n = 15) patients. A 2nd line therapy was performed in 73.9% (n = 17) patients, with imatinib 800mg in 52.9% (n = 9), sunitinib 50mg in 23.5% (n = 4), imatinib 600mg in 17.6% (n = 3), surgery in 5.9% (n = 1) patients. A 3rd line was performed in 52.2% (n = 12), with sunitinib 50mg in 41.7% (n = 5), imatinib 400mg 25% (n = 3), sunitinib 37.5mg in 25% (n = 3), and imatinib 800mg in 8.3% (n = 1) of these patients. A 4th line treatment was made in 21.7% (n = 5) patients. Grade 3 or 4 toxicities have become more frequent in the course of successive therapeutic lines: anemia, neutropenia, nausea, dyspeptic symptoms, hypertension. Median overall survival was 6.9 years (3.2 to 10.6; 95% CI). Considering a survival greater than 5 years as a long-survival in advanced GIST, we observed 47.8% (n = 11) long-survivors. However, no statistically significant differences were found between long and non-long survivors. Conclusion: Comparing to literature, these patients presented a superior overall survival, but KIT exon 11 mutation and long-survivors were mostly similar. The long-term impact of this treatment should be evaluated in order to better understand clinical, pathological and molecular features of this disease.