Efficacy and Safety of CAP7.1 as Second-Line Treatment for Advanced Biliary Tract Cancers: Data from a Randomised Phase II Study

Autor: Johannes Meiler, Victor Rodriguez-Laval, Steffen Heeg, Anja A. Kühl, Ruza Arsenic, Ulrich-Frank Pape, Karel Caca, Stefan Kasper, Holger Jansen, Arndt Vogel, Oswald Burkhard, Petra Büchner-Steudel, Marianne Sinn, Peter Treasure, Nalân Utku, Lothar Müller
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cancers
Volume 12
Issue 11
Cancers, Vol 12, Iss 3149, p 3149 (2020)
ISSN: 2072-6694
DOI: 10.3390/cancers12113149
Popis: CAP7.1 is a novel topoisomerase II inhibitor, converted to active etoposide via carboxylesterase 2 (CES2), with signals of efficacy in treatment-refractory solid tumours. In a Phase II trial, 27 patients with advanced biliary tract cancers (BTC) were randomised 1:1 to CAP7.1 plus best supportive care (BSC), or BSC alone, with crossover to CAP7.1 upon disease progression. The primary objective was disease control rate (DCR) following 28-day cycles of CAP7.1 (200/150 mg/m2
iv), or BSC until progression. Secondary objectives included progression-free survival (PFS), time-to-treatment failure (TTF), overall survival (OS) and safety. Fourteen patients received CAP7.1 and 13 BSC. DCR favoured CAP7.1 vs. BSC (50% vs. 20%
treatment difference: 30%, 95%CI &minus
18.44, 69.22, full analysis set [FAS]), with disease progression in 40% vs. 70%, respectively. Significantly longer median PFS was achieved for CAP7.1 vs. BSC: 66 vs. 39 days, respectively (hazard ratio [HR] 0.31
95%CI 0.11, 0.86
p = 0.009
FAS). Similar trends were observed for TTF and OS. CES2-positive patients had longer median PFS (158 vs. 56 days) and OS (228 vs. 82 days) vs. CES2-negative patients. Adverse events were predictable, dose-dependent and consistent with those previously observed with etoposide. These efficacy and safety findings in second-line BTC warrant further clinical investigation of CAP7.1.
Databáze: OpenAIRE
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