Circulating Tumor DNA Predicts Outcome from First-, but not Second-line Treatment and Identifies Melanoma Patients Who May Benefit from Combination Immunotherapy
Gabriela Marsavela, Jenny Lee, Leslie Calapre, Stephen Q Wong, Michelle R Pereira, Ashleigh C McEvoy, Anna L Reid, Cleo Robinson, Lydia Warburton, Afaf Abed, Muhammad A Khattak, Tarek M Meniawy, Sarah-Jane Dawson, Shahneen Sandhu, Matteo S Carlino, Alexander M Menzies, Richard A Scolyer, Georgina Long, Benhur Amanuel, Michael Millward Show all
CLINICAL CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2020
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 t..View full abstract
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Awarded by National Health and Medical Research Council [NHMRC]
Awarded by Cancer Council
This work was supported by the National Health and Medical Research Council [NHMRC; APP1117911, to M.R. Ziman, M. Millward, B. Amanuel, H. Rizos, E.S. Gray, M.A. Khattak; APP1053792 and APP1107126, to S.Q. Wong, S. Sandhu, S-J. Dawson; APP1128951, to H. Rizos, M.S. Carlino, A.M. Menzies; and APP1119059 and Program Grant, to R.A. Scolyer and G.V. Long]; the Cancer Council (APP1100249, to E.S. Gray, M.R. Ziman, M. Millward); the Department of Health Western Australia (to M.Z., E.G., M.M., M.K., B.A;.no grant number); the Spinnaker Foundation (to M.R. Ziman, E.S. Gray, M. Millward, M.A. Khattak, B. Amanuel; no grant number); the Perpetual Foundation (to M.R. Ziman, E.S. Gray, M. Millward, M.A. Khattak, B. Amanuel; no grant number); the Merck Sharp & Dohme Investigator Studies Program (grant provided to M.A. Khattak; no grant number); the ECU Early Career Research (grant to L. Calapre; no grant number); fellowships from the Cancer Research Trust and Cancer Council WA (to E.S. Gray; no grant number); fellowship from the Western Australia Health Translational Network (to A.C. McEvoy; no grant number); Senior Research fellowship from NHMRC (to H. Rizos; no grant number); midcareer fellowship from the Victorian Cancer Agency (to S.Q. Wong; no grant number); fellowship from Cancer Institute NSW and Melanoma Institute Australia (to A.M. Menzies; no grant number). G.V. Long is supported by the University of Sydney Medical Foundation. G. Marsavela is supported by a scholarship from the School of Medical and Health Sciences at Edith Cowan University. We would like to thank the patients with melanoma for their participation and support of the study. We also thank Aaron Beasley, Jamie Freeman, Paula van Miert, Mike Morici, Danielle Bartlett, and Pauline Zaenker for their help in the collection and processing of blood samples from patients and healthy controls. Furthermore, we extend our thanks to Dr. Tindaro Giardina from Pathwest for assistance with mutation profiling of tumors and Dr. Johnny Lo for helping with part of the statistical analysis. Assistance from colleagues at Melanoma Institute Australia and the Ainsworth Foundation is also gratefully acknowledged.