ArticlePancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]2020
Phase 1 trial of Vismodegib and Erlotinib combination in metastatic pancreatic cancer.
Article in Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Hedgehog signaling drives glial cell plasticity and oncogenic reprogramming in gastroenteropancreatic neuroendocrine neoplasms.Molecular cancer · 2026Article
- EZH2 inhibitor and Vismodegib synergistically inhibit the growth and metastasis of medulloblastoma.Medical oncology (Northwood, London, England) · 2025Article
- Current Status of Hedgehog Signaling Inhibitors.Current topics in medicinal chemistry · 2024Review
- Recent advances in targeted therapy for pancreatic adenocarcinoma.World journal of gastrointestinal oncology · 2023Review
- Signaling pathways in the regulation of cancer stem cells and associated targeted therapy.MedComm · 2022Review
- Cancer-associated fibroblasts in pancreatic cancer: new subtypes, new markers, new targets.The Journal of pathology · 2022Review
- Pancreatic cancer in 2021: What you need to know to win.World journal of gastroenterology · 2021Review
- The Role of Smoothened-Dependent and -Independent Hedgehog Signaling Pathway in Tumorigenesis.Biomedicines · 2021Review
- Review
- The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and PerformancePharmaceutics · 2021Article
- Targeting the Stroma in the Management of Pancreatic Cancer.Frontiers in oncology · 2021Review
- Clinical efficacy evaluation of Erlotinib Combined with Concurrent Chemoradiotherapy in the treatment of locally advanced Pancreatic Cancer.Pakistan journal of medical sciencesArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
30 authors at 6 institutions in 2 countries.
Funding
Abstract
BACKGROUND/
objectivesInterplay between the Hedgehog (HH) and epidermal growth factor receptor (EGFR) pathways modulating the outcome of their signaling activity have been reported in various cancers including pancreatic ductal adenocarcinoma (PDAC). Therefore, simultaneous targeting of these pathways may be clinically beneficial. This Phase I study combined HH and EGFR inhibition in metastatic PDAC patients.
methodsCombined effects of HH and EGFR inhibition using Vismodegib and Erlotinib with or without gemcitabine in metastatic solid tumors were assessed by CT. Another cohort of patients with metastatic PDAC was evaluated by FDG-PET and tumor biopsies-derived biomarkers.
resultsTreatment was well tolerated with the maximum tolerated dose cohort experiencing no grade 4 toxicities though 25% experienced grade 3 adverse effects. Recommended phase II dose of Vismodegib and Erlotinib were each 150 mg daily. No tumor responses were observed although 16 patients achieved stable disease for 2-7 cycles. Paired biopsy analysis before and after first cycle of therapy in PDAC patients showed reduced GLI1 mRNA, phospho-GLI1 and associated HH target genes in all cases. However, only half of the cases showed reduced levels of desmoplasia or changes in fibroblast markers. Most patients had decreased phospho-EGFR levels.
conclusionsVismodegib and Erlotinib combination was well-tolerated although overall outcome in patients with metastatic PDAC was not significantly impacted by combination treatment. Biomarker analysis suggests direct targets inhibition without significantly affecting the stromal compartment. These findings conflict with pre-clinical mouse models, and thus warrant further investigation into how upstream inhibition of these pathways is circumvented in PDAC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.