A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients

Background: The aim of this study was to determine whether checkpoint kinase 1 inihibitor (CHK1), LY2603618, and gemcitabine prolong overall survival (OS) compared to gemcitabine alone in patients with unresectable pancreatic cancer. Methods: Patients with Stage II-IV locally advanced or metastatic...

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Autores: Laquente, Berta, Lopez Martin, Jose, Richards, Donald, Illerhaus, Gerald, Chang, David Z., Kim, George, Stella, Philip, Richel, Dirk, Szcylik, Cezary, Cascinu, Stefano, Frassineti, G. L., Ciuleanu, Tudor, Hurt, Karla, Hynes, Scott, Lin, Ji, Lin, Aimee Bence, Hoff, Daniel Von, Calvo, Emiliano
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/124332
Acceso en línea:https://hdl.handle.net/2445/124332
Access Level:acceso abierto
Palabra clave:Càncer de pàncrees
Quimioteràpia
Pancreas cancer
Chemotherapy
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spelling A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patientsLaquente, BertaLopez Martin, JoseRichards, DonaldIllerhaus, GeraldChang, David Z.Kim, GeorgeStella, PhilipRichel, DirkSzcylik, CezaryCascinu, StefanoFrassineti, G. L.Ciuleanu, TudorHurt, KarlaHynes, ScottLin, JiLin, Aimee BenceHoff, Daniel VonCalvo, EmilianoCàncer de pàncreesQuimioteràpiaPancreas cancerChemotherapyBackground: The aim of this study was to determine whether checkpoint kinase 1 inihibitor (CHK1), LY2603618, and gemcitabine prolong overall survival (OS) compared to gemcitabine alone in patients with unresectable pancreatic cancer. Methods: Patients with Stage II-IV locally advanced or metastatic pancreatic cancer were randomized (2: 1) to either 230 mg of LY2603618/1000 mg/m2 gemcitabine combined or 1000 mg/m2 gemcitabine alone. OS was assessed using both a Bayesian augment control model and traditional frequentist analysis for inference. Progression-free survival (PFS), overall response rate (ORR), duration of response, pharmacokinetics (PK), and safety (Common Terminology Criteria for Adverse Events [AEs] v 3.0) were also evaluated. Results: Ninety-nine patients (n = 65, LY2603618/gemcitabine; n = 34, gemcitabine) were randomized (intent-to-treat population). The median OS (months) was 7.8 (range, 0.3-18.9) with LY2603618/gemcitabine and 8.3 (range, 0.8-19.1+) with gemcitabine. Similarly, in a Bayesian analysis, the study was not positive since the posterior probability that LY2603618/gemcitabine was superior to gemcitabine in improving OS was 0.3, which did not exceed the prespecified threshold of 0.8. No significant improvements in PFS, ORR, or duration of response were observed. Drug-related treatment-emergent AEs in both arms included nausea, thrombocytopenia, fatigue, and neutropenia. The severity of AEs with LY2603618/gemcitabine was comparable to gemcitabine. The LY2603618 exposure targets (AUC((0-infinity)) >= 21,000 ng hr/mL and C-max >= 2000 ng/mL) predicted for maximum pharmacodynamic response were achieved after 230 mg of LY2603618. Conclusions: LY2603618/gemcitabine was not superior to gemcitabine for the treatment of patients with pancreatic cancer.BioMed Central2018201820172018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion9 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/124332Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1186/s12885-017-3131-xBMC Cancer, 2017, vol. 17, num. 137https://doi.org/10.1186/s12885-017-3131-xcc by (c) Laquente et al., 2017http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1243322026-05-29T05:05:01Z
dc.title.none.fl_str_mv A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients
title A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients
spellingShingle A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients
Laquente, Berta
Càncer de pàncrees
Quimioteràpia
Pancreas cancer
Chemotherapy
title_short A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients
title_full A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients
title_fullStr A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients
title_full_unstemmed A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients
title_sort A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients
dc.creator.none.fl_str_mv Laquente, Berta
Lopez Martin, Jose
Richards, Donald
Illerhaus, Gerald
Chang, David Z.
Kim, George
Stella, Philip
Richel, Dirk
Szcylik, Cezary
Cascinu, Stefano
Frassineti, G. L.
Ciuleanu, Tudor
Hurt, Karla
Hynes, Scott
Lin, Ji
Lin, Aimee Bence
Hoff, Daniel Von
Calvo, Emiliano
author Laquente, Berta
author_facet Laquente, Berta
Lopez Martin, Jose
Richards, Donald
Illerhaus, Gerald
Chang, David Z.
Kim, George
Stella, Philip
Richel, Dirk
Szcylik, Cezary
Cascinu, Stefano
Frassineti, G. L.
Ciuleanu, Tudor
Hurt, Karla
Hynes, Scott
Lin, Ji
Lin, Aimee Bence
Hoff, Daniel Von
Calvo, Emiliano
author_role author
author2 Lopez Martin, Jose
Richards, Donald
Illerhaus, Gerald
Chang, David Z.
Kim, George
Stella, Philip
Richel, Dirk
Szcylik, Cezary
Cascinu, Stefano
Frassineti, G. L.
Ciuleanu, Tudor
Hurt, Karla
Hynes, Scott
Lin, Ji
Lin, Aimee Bence
Hoff, Daniel Von
Calvo, Emiliano
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Càncer de pàncrees
Quimioteràpia
Pancreas cancer
Chemotherapy
topic Càncer de pàncrees
Quimioteràpia
Pancreas cancer
Chemotherapy
description Background: The aim of this study was to determine whether checkpoint kinase 1 inihibitor (CHK1), LY2603618, and gemcitabine prolong overall survival (OS) compared to gemcitabine alone in patients with unresectable pancreatic cancer. Methods: Patients with Stage II-IV locally advanced or metastatic pancreatic cancer were randomized (2: 1) to either 230 mg of LY2603618/1000 mg/m2 gemcitabine combined or 1000 mg/m2 gemcitabine alone. OS was assessed using both a Bayesian augment control model and traditional frequentist analysis for inference. Progression-free survival (PFS), overall response rate (ORR), duration of response, pharmacokinetics (PK), and safety (Common Terminology Criteria for Adverse Events [AEs] v 3.0) were also evaluated. Results: Ninety-nine patients (n = 65, LY2603618/gemcitabine; n = 34, gemcitabine) were randomized (intent-to-treat population). The median OS (months) was 7.8 (range, 0.3-18.9) with LY2603618/gemcitabine and 8.3 (range, 0.8-19.1+) with gemcitabine. Similarly, in a Bayesian analysis, the study was not positive since the posterior probability that LY2603618/gemcitabine was superior to gemcitabine in improving OS was 0.3, which did not exceed the prespecified threshold of 0.8. No significant improvements in PFS, ORR, or duration of response were observed. Drug-related treatment-emergent AEs in both arms included nausea, thrombocytopenia, fatigue, and neutropenia. The severity of AEs with LY2603618/gemcitabine was comparable to gemcitabine. The LY2603618 exposure targets (AUC((0-infinity)) >= 21,000 ng hr/mL and C-max >= 2000 ng/mL) predicted for maximum pharmacodynamic response were achieved after 230 mg of LY2603618. Conclusions: LY2603618/gemcitabine was not superior to gemcitabine for the treatment of patients with pancreatic cancer.
publishDate 2017
dc.date.none.fl_str_mv 2017
2018
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/124332
url https://hdl.handle.net/2445/124332
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s12885-017-3131-x
BMC Cancer, 2017, vol. 17, num. 137
https://doi.org/10.1186/s12885-017-3131-x
dc.rights.none.fl_str_mv cc by (c) Laquente et al., 2017
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Laquente et al., 2017
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 9 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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