O2-5-3Regorafenib as second line therapy for imatinib-resistant gastrointestinal stromal tumor (GIST): A phase II study

Abstract Background Standard first line treatment for metastatic/recurrent gastrointestinal stromal tumor (GIST) is imatinib; however eventually almost all the GISTs become resistant to imatinib. Secondary mutation in KIT is the most relevant cause of imatinib-resistant, as high as 70% of cases. Sunitinib is the current standard second line treatment for imatinib-resistant GIST with median progression-free survival (PFS) of 24.6 weeks; however, in a preclinical study sunitinib is not active for approximately half of secondary mutant GIST. Regorafenib is active for some secondary mutations resistant to sunitinib in the preclinical study. Therefore, we conducted a prospective phase II study of regorafenib as second line therapy for imatinib-resistant GIST. Method Patients with imatinib-resistant metastatic/recurrent GIST were eligible for the current study. Other key inclusion criteria included patients with ECOG performance status of 0-1 and adequate organ function. Patients treated with sunitinib were excluded. The primary endpoint was PFS rate at 24 weeks. Tumor response, safety, and biomarkers were also analyzed. Results A total of 38 patients were enrolled as planned. Median age was 64.5 (39 - 80). Twenty-five patients were male. Primary site was stomach in 17, small intestine in 16. Best overall response was PR for 5 (13%), SD for 24 (63%) and PD for 6 (16%) patients, with response rate of 13%. Grade 3 or more adverse events (AE) were observed in 25 (66%) patients. Common grade 3 or more AE were hand-foot syndrome (n = 9), hypertension (n = 9), hepatotoxicity (n = 4), thrombocytopenia (n = 2), and proteinuria (n = 2). There was one treatment-related death (cerebral attack). The primary endpoint of PFS will be presented at the conference. Conclusion Regorafenib demonstrated promising activity in patients with imatinib-resistant GIST as second line therapy with acceptable toxicity.