Galunisertib plus gemcitabine vs. gemcitabine for first-line treatment of patients with unresectable pancreatic cancer
Melisi, Davide (University of Verona, Piazzale Ludovico Antonio Scuro)
García-Carbonero, Rocío (Hospital Universitario 12 de Octubre (Madrid))
Macarulla Mercadé, Teresa (Vall d'Hebron Institut d'Oncologia)
Pezet, Denis (Centre Hospitalier Universitaire)
Deplanque, Gael (Hôpital Riviera-Chablais)
Fuchs, Martin (Klinikum Bogenhausen, Städtisches Klinikum München GmbH, Englschalkinger Road 77, 81925 Munich, Germany)
Trojan, Jorg (Goethe University Medical Center)
Oettle, Helmut (Onkologische und Hämatologische Schwerpunktpraxis, Friedrichshafen, Germany)
Kozloff, Mark (Ingalls Memorial Hospital)
Cleverly, Ann (Eli Lilly and Company, Erl Wood Manor, Windlesham)
Smith, Claire (formerly of Eli Lilly and Company)
Estrem, Shawn T. (Eli Lilly and Company, Lilly Corporate Center)
Gueorguieva, Ivelina (Eli Lilly and Company, Erl Wood Manor, Windlesham)
Lahn, Michael M. F. (Wisconsin Ave., #8008, Bethesda, MD 20815 USA)
Blunt, Al (Advaxis, Inc)
Benhadji, Karim A. (Eli Lilly and Company)
Tabernero, Josep (Universitat Autònoma de Barcelona. Departament de Medicina)
Universitat Autònoma de Barcelona

Fecha:	2018
Resumen:	Galunisertib is the first-in-class, first-in-human, oral small-molecule type I transforming growth factor-beta receptor (ALK5) serine/threonine kinase inhibitor to enter clinical development. The effect of galunisertib vs. placebo in patients with unresectable pancreatic cancer was determined. This was a two-part, multinational study: phase 1b was a non-randomised, open-label, multicentre, and dose-escalation study; phase 2 was a randomised, placebo- and Bayesian-augmented controlled, double-blind study in patients with locally advanced or metastatic pancreatic adenocarcinoma considered candidates for first-line chemotherapy with gemcitabine. Patients were randomised 2:1 to galunisertib-gemcitabine (N = 104) or placebo-gemcitabine (N = 52). Gemcitabine dose was 1000 mg/m 2 QW. Primary endpoints for phases 1b and 2, respectively, were phase 2 dose and overall survival. Secondary objectives included tolerability and biomarkers. Dose-escalation suggested a 300-mg/day dose. Primary objective was met: median survival times were 8. 9 and 7. 1 months for galunisertib and placebo, respectively (hazard ratio [HR] = 0. 79 [95% credible interval: 0. 59-1. 09] and posterior probability HR < 1 = 0. 93). Lower baseline biomarkers macrophage inflammatory protein-1-alpha and interferon-gamma-induced protein 10 were associated with galunisertib benefit. Galunisertib-gemcitabine combination improved overall survival vs. gemcitabine in patients with unresectable pancreatic cancer, with minimal added toxicity. Future exploration of galunisertib in pancreatic cancer is ongoing in combination with durvalumab.
Nota:	Altres ajuts: This study was sponsored by Eli Lilly and Company, IN, USA.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Cancer immunotherapy ; Prognostic markers ; Predictive markers
Publicado en:	British Journal of Cancer, Vol. 119 (october 2018) , p. 1208-1214, ISSN 1532-1827

DOI: 10.1038/s41416-018-0246-z
PMID: 30318515

7 p, 1.3 MB

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