Clinical and biological markers predictive of treatment response associated with metastatic pancreatic adenocarcinoma.

Autor: Dayimu A; Clinical Trials Unit, Department of Oncology, University of Cambridge, Cambridge, UK., Di Lisio L; Cancer Molecular Diagnostics Laboratory, Department of Oncology, University of Cambridge, Cambridge, UK., Anand S; Cancer Molecular Diagnostics Laboratory, Department of Oncology, University of Cambridge, Cambridge, UK., Roca-Carreras I; Cancer Molecular Diagnostics Laboratory, Department of Oncology, University of Cambridge, Cambridge, UK., Qian W; Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Al-Mohammad A; Oncology Department, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Basu B; Department of Oncology, University of Cambridge, Cambridge, UK., Valle JW; University of Manchester and The Christie NHS Foundation Trust, Manchester, UK., Jodrell D; Department of Oncology, University of Cambridge, Cambridge, UK., Demiris N; Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Department of Statistics, Athens University of Economics and Business, Athens, Greece., Corrie P; Oncology Department, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. philippa.corrie@nhs.net.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2023 May; Vol. 128 (9), pp. 1672-1680. Date of Electronic Publication: 2023 Feb 22.
DOI: 10.1038/s41416-023-02170-9
Abstrakt: Background: Chemotherapy for metastatic pancreatic adenocarcinoma (PDAC) offers limited benefits, but survival outcomes vary. Reliable predictive response biomarkers to guide patient management are lacking.
Methods: Patient performance status, tumour burden (determined by the presence or absence of liver metastases), plasma protein biomarkers (CA19-9, albumin, C-reactive protein and neutrophils) and circulating tumour DNA (ctDNA) were assessed in 146 patients with metastatic PDAC prior to starting either concomitant or sequential nab-paclitaxel + gemcitabine chemotherapy in the SIEGE randomised prospective clinical trial, as well as during the first 8 weeks of treatment. Correlations were made with objective response, death within 1 year and overall survival (OS).
Results: Initial poor patient performance status, presence of liver metastases and detectable mut KRAS ctDNA all correlated with worse OS after adjusting for the different biomarkers of interest. Objective response at 8 weeks also correlated with OS (P = 0.026). Plasma biomarkers measured during treatment and prior to the first response assessment identified ≥10% decrease in albumin at 4 weeks predicted for worse OS (HR 4.75, 95% CI 1.43-16.94, P = 0.012), while any association of longitudinal evaluation of mut KRAS ctDNA with OS was unclear (β = 0.024, P = 0.057).
Conclusions: Readily measurable patient variables can aid the prediction of outcomes from combination chemotherapy used to treat metastatic PDAC. The role of mut KRAS ctDNA as a tool to guide treatment warrants further exploration.
Clinical Trial Registration: ISRCTN71070888; ClinialTrials.gov (NCT03529175).
(© 2023. The Author(s).)
Databáze: MEDLINE
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