The Clinical Impact of Methylated Homeobox A9 ctDNA in Patients with Non-Resectable Biliary Tract Cancer Treated with Erlotinib and Bevacizumab

Methylated homeobox A9 (meth-HOXA9) is tumor specific and has been suggested as a prognostic biomarker in several types of cancer. ctDNA measured as meth-HOXA9 may be a valuable biomarker in the decision-making process about last-line treatment of biliary tract cancer (BTC). The aim of the study was...

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Bibliographic Details
Published in:Cancers 2022-09, Vol.14 (19), p.4598
Main Authors: Andersen, Line Bechsgaard, Mahler, Marit Sofie Kjær, Andersen, Rikke Fredslund, Jensen, Lars Henrik, Raunkilde, Louise
Format: Article
Language:English
Subjects:
Adverse events
Bevacizumab
Biliary tract
Biomarkers
Cancer
Cancer therapies
Chemotherapy
Decision making
DNA methylation
Dosage and administration
Electronic health records
Erlotinib
Gene expression
Growth factors
Health aspects
Homeobox
Homeobox genes
Homeotic genes
Kinases
Medical prognosis
Medical records
Metastasis
Palliative care
Patient outcomes
Patients
Survival
Toxicity
Tumors
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Summary:Methylated homeobox A9 (meth-HOXA9) is tumor specific and has been suggested as a prognostic biomarker in several types of cancer. ctDNA measured as meth-HOXA9 may be a valuable biomarker in the decision-making process about last-line treatment of biliary tract cancer (BTC). The aim of the study was to investigate the clinical impact of meth-HOXA9 in plasma from patients receiving erlotinib and bevacizumab for late-stage BTC and to investigate the treatment effect and adverse events. Droplet digital PCR was applied to detect meth-HOXA9 in 39 patients. Response rates were registered according to RECIST (1.1) and adverse events according to Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE (4.0)). Endpoints were progression-free survival (PFS), overall survival (OS), response rate, and toxicity. A significant difference in PFS and OS between patients with increasing and non-increasing meth-HOXA9 was detected after one treatment cycle, hazard ratio (HR) 12.4 (p < 0.0001) and HR 2.75 (p = 0.04), respectively. The most common adverse events of erlotinib were fatigue, pain, and rash, and those of bevacizumab were bleeding and wounds. This study found meth-HOXA9 to be negatively associated with survival in patients with late-stage BTC. Hence, meth-HOXA9 may guide early discontinuation of ineffective treatment.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14194598