ArticleBMC cancer2019
Safety and efficacy of afatinib as add-on to standard therapy of gemcitabine/cisplatin in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, phase I trial with an extensive biomarker program.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01679405 (Open-label, Uncontrolled, Multicenter Phase I/Ib Trial to Investigate Safety and Efficacy of BIBW 2992 and Standard Gemcitabine/Cisplatin in Chemo-naïve Patients With Advanced Biliary Tract Adenocarcinoma), which is not on this map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Open-label, Uncontrolled, Multicenter Phase I/Ib Trial to Investigate Safety and Efficacy of BIBW 2992 and Standard Gemcitabine/Cisplatin in Chemo-naïve Patients With Advanced Biliary Tract Adenocarcinoma
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Durvalumab and pembrolizumab in advanced biliary tract cancer: a reconstructed patient-level mimic head-to-head comparative analysis.Frontiers in immunology · 2024Pooled it
- FIGHT-302: first-line pemigatinib vs gemcitabine plus cisplatin for advanced cholangiocarcinoma withFuture oncology (London, England) · 2020Trial
- Adjuvant MUC vaccination with tecemotide after resection of colorectal liver metastases: a randomized, double-blind, placebo-controlled, multicenter AIO phase II trial (LICC).Oncoimmunology · 2020Trial
- Lenvatinib enhances the response of biliary tract cancer to anti-HER2 therapy.Signal transduction and targeted therapy · 2026Article
- Targeted therapies and immunotherapies for unresectable cholangiocarcinoma.Chinese medical journal · 2025Review
- Phase Ia/Ib Study of Afatinib with Capecitabine in Patients with Refractory Solid Tumors and Pancreaticobiliary Cancers.Cancers · 2025Article
- Intrahepatic cholangiocarcinoma patient with epidermal growth factor receptor exon 19 deletion unresponsive to Afatinib monotherapy: a case report.Discover oncology · 2025Article
- Oncogenic Roles of Laminin Subunit Gamma-2 in Intrahepatic Cholangiocarcinoma via Promoting EGFR Translation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Molecular pathology for cholangiocarcinoma: a review of actionable genetic targets and their relevance to adjuvant & neoadjuvant therapy, staging, follow-up, and determination of minimal residual disease.Hepatobiliary surgery and nutrition · 2024Review
- Combination Therapies for Advanced Biliary Tract Cancer.Journal of clinical and translational hepatology · 2023Review
- Genomic profiling of idiopathic peri-hilar cholangiocarcinoma reveals new targets and mutational pathways.Scientific reports · 2023Article
- Uses of Vascular Endothelial Growth Factor C as a Lung Adenocarcinoma Prognostic Biomarker.World journal of oncology · 2023Article
- Outcomes in patients receiving palliative chemotherapy for advanced biliary tract cancer.JHEP reports : innovation in hepatology · 2022Article
- Review
- The Addition of Transarterial Chemoembolization to Palliative Chemotherapy Extends Survival in Intrahepatic Cholangiocarcinoma.Journal of clinical medicine · 2021Article
- Effect of Combining EGFR Tyrosine Kinase Inhibitors and Cytotoxic Agents on Cholangiocarcinoma Cells.Cancer research and treatment · 2021Article
- Promising Molecular Targets for the Targeted Therapy of Biliary Tract Cancers: An Overview.OncoTargets and therapy · 2021Review
- Molecular Features and Targeted Therapies in Extrahepatic Cholangiocarcinoma: Promises and Failures.Cancers · 2020Review
- Systemic treatment options for advanced biliary tract carcinoma.Journal of gastroenterology · 2020Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTo date, the cornerstone of treatment in patients with advanced or metastatic cholangiocarcinoma (CCA) is systemic chemotherapy based on a combination of gemcitabine and a platinum derivative. Other therapeutic approaches including targeted agents and tyrosine kinase inhibitors (TKI) have demonstrated disappointing results, highlighting the complexity of CCA. Recently, drugs aiming at the inhibition of HER-receptors have shown first therapeutic benefit in patients with late stage disease. The aim of this phase I study was to test the dose level toxicities (DLTs), safety and efficacy of afatinib, a highly specific panErbB family receptor TKI, in chemotherapy naive patients with advanced CCA in conjunction with an extensive biomarker program.
methodsAfatinib was administered continuously p. o. as add-on in patients with advanced CCA who received conventional chemotherapy with gemcitabine/cisplatin. A classical 3 + 3 phase I study was employed, while the maximum tolerated dose (MTD) of oral afatinib was determined in a 2 step dose escalation. Safety, overall survival (OS) and progression free survival (PFS) were evaluated for all patients. Finally, a translational biomarker analysis was conducted for the EGFR and VEGF signalling cascades.
resultsOverall, 9 patients were enrolled. Further recruitment was discontinued due to lack of efficacy results of the tested drug in other indications. 30 mg afatinib could be safely administered as add-on to 80% of standard dose gemcitabine/cisplatin. The mOS and mPFS were 7.7 and 6.0 months, respectively. Diarrhoea and haematological disorders were the most common observed AEs. Almost all patients overexpressed EGFR on their tumour tissues, whereas none of them expressed mutations in Exons 18, 19 and 21. Non-responders showed a higher variation of VEGF-C, -D, leptin and sEGFR in their sera.
conclusionsAfatinib failed to show survival benefits in combination with gemcitabine/cisplatin in patients with advanced CCA. Mutational analysis of EGFR and pathways associated with VEGF-C, -D and leptin might show promising results in future studies. CLINICAL TRIALS REGISTRATION: NCT01679405 August, 2012.
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Registered trials
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