Safety and pharmacokinetics (PK) of cabazitaxel (C) in patients (pts) with hepatic impairment (HI).

2538 Background: C studies excluded pts with HI. A Phase I dose-escalation study (NCT01140607) assessed the effect of HI on C PK and safety in pts with advanced solid tumors. Methods: Pts with normal hepatic function (NHF; bilirubin [B] ≤ ULN; aspartate aminotransferase [AST] ≤ ULN), mild (MiHI; B > 1– ≤ 1.5 x ULN or AST > 1.5 x ULN), moderate (ModHI; B > 1.5– ≤ 3 x ULN) or severe (SHI; B > 3–10 x ULN) HI received C dose escalation starting at 25, 20, 10 or 10 mg/m2, respectively. Endpoints were cycle 1 (C1) dose-limiting toxicities (DLTs), safety and PK. Plasma PK were derived by non-compartmental analysis. HI effect was assessed by linear mixed-effects modeling on clearance normalized to body surface area (CL/BSA) and exposure normalized to dose. Results: Pts (43 [6 NHF, 18 MiHI, 12 ModHI, 7 SHI]) had a median age of 60 years (range 18–79); 52% were male; 81% had ECOG performance status 1. Colon and liver tumors were most common (19%; prostate 7%). Maximum tolerated doses (MTD) were 20 (MiHI) and 15 mg/...