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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Circulating tumor DNA predicts outcome from first-, but not second-line treatment and identifies melanoma patients who may benefit from combination immunotherapy
Clinical Cancer Research, Volume 26, No. 22, Year 2020
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Description
Purpose: We evaluated the predictive value of pretreatment ctDNA to inform therapeutic outcomes in patients with metastatic melanoma relative to type and line of treatment. Experimental Design: Plasma circulating tumor DNA (ctDNA) was quantified in 125 samples collected from 110 patients prior to commencing treatment with immune checkpoint inhibitors (ICIs), as first- (n = 32) or second-line (n = 27) regimens, or prior to commencing first-line BRAF/MEK inhibitor therapy (n = 66). An external validation cohort included 128 patients commencing ICI therapies in the first- (N = 77) or second-line (N = 51) settings. Results: In the discovery cohort, low ctDNA (≤20 copies/mL) prior to commencing therapy predicted longer progression-free survival (PFS) in patients treated with first-line ICIs [HR, 0.20; 95% confidence interval (CI) 0.07-0.53; P < 0.0001], but not in the second-line setting. An independent cohort validated that ctDNA is predictive of PFS in the first-line setting (HR, 0.42; 95% CI, 0.22-0.83; P = 0.006), but not in the second-line ICI setting. Moreover, ctDNA prior to commencing ICI treatment was not predictive of PFS for patients pretreated with BRAF/MEK inhibitors in either the discovery or validation cohorts. Reduced PFS and overall survival were observed in patients with high ctDNA receiving anti-PD-1 monotherapy, relative to those treated with combination anti-CTLA-4/anti-PD-1 inhibitors. Conclusions: Pretreatment ctDNA is a reliable indicator of patient outcome in the first-line ICI treatment setting, but not in the second-line ICI setting, especially in patients pretreated with BRAF/MEK inhibitors. Preliminary evidence indicated that treatment-naïve patients with high ctDNA may preferentially benefit from combined ICIs. © 2020 American Association for Cancer Research.
Authors & Co-Authors
Khattak, Muhammad Adnan
Australia, Perth
Edith Cowan University
Australia, Perth
Fiona Stanley Hospital
Australia, Perth
The University of Western Australia
Sandhu, Shahneen K.
Australia, Melbourne
Peter Maccallum Cancer Centre
Menzies, Alexander M.
Australia, Sydney
The University of Sydney
Australia, Sydney
Sydney Cancer Centre
Scolyer, Richard A.
Australia, Sydney
The University of Sydney
Australia, Sydney
Royal Prince Alfred Hospital
Long, Georgina V.
Australia, Sydney
The University of Sydney
Australia, Sydney
Sydney Cancer Centre
Millward, Michael J.
Australia, Perth
Sir Charles Gairdner Hospital
Australia, Perth
The University of Western Australia
Ziman, Mel
Australia, Perth
Edith Cowan University
Australia, Perth
The University of Western Australia
Gray, Elin Solomonovna
Unknown Affiliation
Statistics
Citations: 34
Authors: 8
Affiliations: 10
Identifiers
Doi:
10.1158/1078-0432.CCR-20-2251
ISSN:
10780432
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Study Design
Cohort Study