The prognostic impact of circulating tumour dna in melanoma patients treated with systemic therapies—beyond braf mutant detection

Authors

Gabriela Marsavela, Edith Cowan UniversityFollow
Peter A. Johansson
Michelle R. Pereira, Edith Cowan University
Ashleigh C. McEvoy, Edith Cowan UniversityFollow
Anna L. Reid, Edith Cowan UniversityFollow
Cleo Robinson
Lydia Warburton, Edith Cowan UniversityFollow
Muhammad A. Khattak, Edith Cowan UniversityFollow
Tarek M. Meniawy, Edith Cowan UniversityFollow
Benhur Amanuel, Edith Cowan UniversityFollow
Michael Millward
Nicholas K. Hayward
Melanie R. Ziman, Edith Cowan UniversityFollow
Elin S. Gray, Edith Cowan UniversityFollow
Leslie Calapre, Edith Cowan UniversityFollow

Document Type

Journal Article

Publication Title

Cancers

Volume

12

Issue

12

First Page

1

Last Page

13

Publisher

MDPI

School

School of Medical and Health Sciences

RAS ID

32735

Funders

Funding Information: https://www.mdpi.com/2072-6694/12/12/3793/htm

Grant Number

NHMRC Number : 1117911

Grant Link

http://purl.org/au-research/grants/nhmrc/1117911

Comments

Marsavela, G., Johansson, P. A., Pereira, M. R., McEvoy, A. C., Reid, A. L., Robinson, C., ... Calapre, L. (2020). The prognostic impact of circulating tumour DNA in melanoma patients treated with systemic therapies—beyond BRAF mutant detection. Cancers, 12(12), article 3793. https://doi.org/10.3390/cancers12123793

Abstract

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. In this study, we evaluated the predictive value of circulating tumour DNA (ctDNA) to inform therapeutic outcomes in metastatic melanoma patients receiving systemic therapies. We analysed 142 plasma samples from metastatic melanoma patients prior to commencement of systemic therapy: 70 were treated with BRAF/MEK inhibitors and 72 with immunotherapies. Patient-specific droplet digital polymerase chain reaction assays were designed for ctDNA detection. Plasma ctDNA was detected in 56% of patients prior to first-line anti-PD1 and/or anti-CTLA-4 treatment. The detection rate in the immunotherapy cohort was comparably lower than those with BRAF inhibitors (76%, p = 0.0149). Decreasing ctDNA levels within 12 weeks of treatment was strongly concordant with treatment response (Cohen’s k = 0.798, p < 0.001) and predictive of longer progression free survival. Notably, a slower kinetic of ctDNA decline was observed in patients treated with immunotherapy compared to those on BRAF/MEK inhibitors. Whole exome sequencing of ctDNA was also conducted in 9 patients commencing anti-PD-1 therapy to derive tumour mutational burden (TMB) and neoepitope load measurements. The results showed a trend of high TMB and neoepitope load in responders compared to non-responders. Overall, our data suggest that changes in ctDNA can serve as an early indicator of outcomes in metastatic melanoma patients treated with systemic therapies and therefore may serve as a tool to guide treatment decisions.

DOI

10.3390/cancers12123793

Related Publications

Marsavela, A. (2021). Assessment of the clinical validity of ctDNA Analysis for melanoma management. https://ro.ecu.edu.au/theses/2407

Creative Commons License

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