Document Type

Journal Article

Publication Title

Cancers

Volume

13

Issue

7

Publisher

MDPI

School

Centre for Precision Health / School of Medical and Health Sciences

RAS ID

35840

Funders

Melanoma Institute Australia / Sydney Vital Translational Cancer Research Centre / National Health and Medical Research Council / Cancer Council of Western Australia / University of Sydney Medical Foundation

Comments

Park, J. J., Diefenbach, R. J., Byrne, N., Long, G. V., Scolyer, R. A., Gray, E. S., ... Rizos, H. (2021). Circulating tumor DNA reflects uveal melanoma responses to protein kinase C inhibition. Cancers, 13(7), article 1740. https://doi.org/10.3390/cancers13071740

Abstract

The prognosis for patients with UM is poor, and recent clinical trials have failed to prolong overall survival (OS) of these patients. Over 95% of UM harbor activating driver mutations, and this allows for the investigation of ctDNA. In this study, we investigated the value of ctDNA for adaptive clinical trial design in metastatic UM. Longitudinal plasma samples were analyzed for ctDNA in 17 metastatic UM patients treated with PKCi-based therapy in a phase 1 clinical trial setting. Plasma ctDNA was assessed using digital droplet PCR (ddPCR) and a custom melanoma gene panel for targeted next generation sequencing (NGS). Baseline ctDNA strongly correlated with baseline lactate dehydrogenase (LDH) (p < 0.001) and baseline disease burden (p = 0.002). Early during treatment (EDT) ctDNA accurately predicted patients with clinical benefit to PKCi using receiver operator characteristic (ROC) curves (AUC 0.84, [95% confidence interval 0.65–1.0, p = 0.026]). Longitudinal ctDNA assessment was informative for establishing clinical benefit and detecting disease progression with 7/8 (88%) of patients showing a rise in ctDNA and targeted NGS of ctDNA revealed putative resistance mechanisms prior to radiological progression. The inclusion of longitudinal ctDNA monitoring in metastatic UM can advance adaptive clinical trial design.

DOI

10.3390/cancers13071740

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Research Themes

Health

Priority Areas

Prevention, detection and management of cancer and other chronic diseases

Included in

Diseases Commons

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