A QTc study of cabazitaxel in patients with advanced solid tumors.

• DOI: 10.1200/jco.2012.30.15_suppl.e15115
• Publication Date: 2020-03-11T15:15:23Z
• Authors: James Lloyd Wade; Shaker R. Dakhil; Ari David Baron; Sylvie Rottey; Frederick E. Millard; Gedske Daugaard; Jean-Pascal H. Ma...; William A. Conkright; Sunil Sharma; Patricia M.M.B. S...; Jeffrey Yachnin; Lisa Sengeløv; Peter van Veldhuizen; Sanjiv S. Agarwala; TX Quyen Nguyen; Mustapha Chadjaa; Pierre Maison-Bla...
• Keywords: Cabazitaxel; Concomitant; Clinical endpoint; Mitoxantrone

e15115 Background: Cabazitaxel (Cbz) improves overall survival in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel failure, compared mitoxantrone (HR 0.70; 95% CI 0.59–0.83; p<0.0001). Following Cbz approval for the treatment of mCRPC, this study was undertaken to evaluate any effect on QTc interval. Methods: This prospective, multinational, open-label (NCT01087021) enrolled pts advanced solid tumors (without other therapeutic options). 25 mg/m² IV administered Day 1 Q3W. and ECG intervals were assessed Cycle 1. Triplicate ECGs obtained from 12-lead Holter recordings concomitant serial blood samples collected pharmacokinetic (PK) analysis. The primary endpoint change baseline corrected interval (according Fridericia formula [QTcF]). Results: A total 96 enrolled; 32 under original protocol (6-h Holter) 64 following amendment 1, which extended PK monitoring (24-h Holter). Median age 63 yrs (69.8% male), 30.5% 57.9% ECOG PS 0 respectively; 33 (34.4%) had cancer. Screening abnormal but not clinically significant 39.6% pts. majority (n=65) received ≥ 3 cycles; safety parameters evaluated 95 94 pts, respectively. In 24-h group (n=63), maximum least squares (LS) mean QTcF 4.8 msec (90% 2.1–7.5), returning by 24 h. Similar results observed population (n=94). At C max , concentration no baseline; (CV%) (n=91) AUC (n=92) 276 ng/ml (63%) 1245 ng.h/ml (82%). LS heart rate increased up h remained < 10 beats per minute. most common grade 3/4 AEs neutropenia (27.4%), febrile (12.6%), fatigue (12.6%) dehydration (5.3%). No cardiac reported. Of 6 deaths reported, (infection) drug related. Conclusions: tumors. profile is consistent previous findings taxane-based therapies.