ID #985 Early results of a phase Ib study of the SGLT2 inhibitor dapagliflozin plus chemotherapy in relapsed/refractory brain and solid tumors

Abstract Introduction Glucose utilization by tumors has been studied as a potential target to exploit in treating malignancies. FDG-PET has demonstrated that FDG uptake in brain tumors positively correlates with brain tumor grade and poorer prognosis and is also used as modality for staging in solid tumors due to increased glycolytic index of the tumors. Sodium glucose cotransporter 2 inhibitors (SGLT2i), such as dapagliflozin, lower serum glucose by inhibiting reabsorption in the renal tubules.Additionally, tumors also express functional SGLT2 on their cell surface, indicating that SGLT2i may have direct glycolytic inhibitory effects on brain and solid tumors. Methods Patients with relapsed/refractory brain or solid tumors with no curative options were enrolled to a 12-week trial of dapagliflozin in addition to cytotoxic chemotherapy including BCNU (100 mg/m2 every 6 weeks) for brain tumor patients and topotecan (0.75 mg/m2) with cyclophosphamide (250 mg/m2) on days 1-5 of 21 day cycles for solid tumor patients. Patients aged 6-12 years received a fixed dapagliflozin dose of 5 mg daily, while patients aged 11-21 years began at 5 mg and escalated to 10 mg after two weeks if well tolerated. Imaging was performed every 6 weeks. Results To date, we have enrolled four patients aged 7-17 years (two anaplastic ependymomas, one high grade glioma, one Ewing sarcoma). Two patients had stable disease (ependymoma and Ewing sarcoma) and two had progressive disease. There were no Grade 3 or 4 toxicities related to dapagliflozin. One patient had Grade 1 ketoacidosis in the setting of poor caloric intake. Of note, one patient with anaplastic ependymoma continued dapagliflozin and BCNU for 1 year with continued stable disease. Conclusions Adding SGLT2i with dapagliflozin to cytotoxic chemotherapy for relapsed/refractory brain and solid tumors has thus far been well tolerated and two patients demonstrated stable disease. Enrollment in this study is ongoing.