LAUSR

e16118 Background: Median overall survival (OS) in advanced adrenocortical (ACC) is only 12-15 months. Previous clinical trials with oral multi-kinase inhibitors (MKI) were negative likely due to inadvertent drug interaction with mitotane. Objective: To investigate the potential of cabozantinib (CABO) monotherapy in ACC patients. Methods: Retrospective cohort study at three referral centers for ACC (U.S. and Germany). Results: Fifteen patients (13 female) with progressive disease after mitotane (14/15 patients) and three (median; range 0-8) further systemic therapies were treated with 60 mg (20-140) CABO. Mitotane had been discontinued in all patients, in 11/15 patients mitotane was stopped > 270 days before CABO treatment or plasma concentration documented to be < 2 mg/L. Adverse events (AE) of grade 1/2 and 3 were observed in 12 and 2 patients, respectively and consistent with the known safety profile of CABO. Best response was partial response in 3, stable disease in 4 and progressive disease in 8 patients. Progression-free survival (PFS) of > 4 months (PFS4) was observed in 7 patients. Median PFS and OS was 12 and 41 weeks, respectively. Two single center phase II trials of CABO in advanced ACC in the U.S. (NCT03370718) and Germany (NCT03612232) will accrue 18 and 37 patients, respectively. Mitotane discontinuation and plasma concentrations < 2 mg/L are key inclusion criteria. The primary endpoint is PFS4. Conclusions: Cabozantinib monotherapy appears to be safe and active as a monotherapy in advanced ACC. Two parallel phase II trials will investigate CABO prospectively while controlling for drug interaction with mitotane.