Clinical and biological markers predictive of treatment response associated with metastatic pancreatic adenocarcinoma
Dayimu, A. Di Lisio, L. Anand, S. Roca-Carreras, I. Qian, W. Al-Mohammad, A. Basu, B. Valle, Juan W Jodrell, D. Demiris, N.
Dayimu, A.
Di Lisio, L.
Anand, S.
Roca-Carreras, I.
Qian, W.
Al-Mohammad, A.
Basu, B.
Valle, Juan W
Jodrell, D.
Demiris, N.
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Abstract
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 mutKRAS 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 mutKRAS 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 mutKRAS ctDNA as a tool to guide treatment warrants further exploration.
Description
Date
2023
Publisher
Collections
Keywords
Type
Article
Citation
Dayimu A, Di Lisio L, Anand S, Roca-Carreras I, Qian W, Al-Mohammad A, et al. Clinical and biological markers predictive of treatment response associated with metastatic pancreatic adenocarcinoma. British journal of cancer. 2023 Feb 22. PubMed PMID: 36813867. Epub 2023/02/23. eng.