Phase 2 study of vismodegib, a hedgehog inhibitor, combined with gemcitabine and nab-paclitaxel in patients with untreated metastatic pancreatic adenocarcinoma.
Br J Cancer
; 122(4): 498-505, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31857726
ABSTRACT
BACKGROUND:
The Hedgehog (Hh) signalling pathway is overexpressed in pancreatic ductal adenocarcinoma (PDA). Preclinical studies have shown that Hh inhibitors reduce pancreatic cancer stem cells (pCSC), stroma and Hh signalling.METHODS:
Patients with previously untreated metastatic PDA were treated with gemcitabine and nab-paclitaxel. Vismodegib was added starting on the second cycle. The primary endpoint was progression-free survival (PFS) as compared with historical controls. Tumour biopsies to assess pCSC, stroma and Hh signalling were obtained before treatment and after cycle 1 (gemcitabine and nab-paclitaxel) or after cycle 2 (gemcitabine and nab-paclitaxel plus vismodegib).RESULTS:
Seventy-one patients were enrolled. Median PFS and overall survival (OS) were 5.42 months (95% confidence interval [CI] 4.37-6.97) and 9.79 months (95% CI 7.85-10.97), respectively. Of the 67 patients evaluable for response, 27 (40%) had a response 26 (38.8%) partial responses and 1 complete response. In the tumour samples, there were no significant changes in ALDH + pCSC following treatment.CONCLUSIONS:
Adding vismodegib to chemotherapy did not improve efficacy as compared with historical rates observed with chemotherapy alone in patients with newly diagnosed metastatic pancreatic cancer. This study does not support the further evaluation of Hh inhibitors in this patient population. TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT01088815.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Piridinas
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Protocolos de Quimioterapia Combinada Antineoplásica
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Carcinoma Ductal Pancreático
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Anilidas
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Br J Cancer
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos