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Circulating Cell-free DNA as a Prognostic Biomarker in Patients with Advanced ALK+ Non–small Cell Lung Cancer in the Global Phase III ALEX Trial

PURPOSE: We retrospectively assessed prognostic value of circulating cell-free DNA (cfDNA) using data from the phase III ALEX study in treatment-naïve, advanced ALK+ non–small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomized to receive twice-daily alectinib 600 mg (n = 152) o...

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Autores principales: Dziadziuszko, Rafal, Peters, Solange, Mok, Tony, Camidge, D. Ross, Gadgeel, Shirish M., Ou, Sai-Hong Ignatius, Konopa, Krzysztof, Noé, Johannes, Nowicka, Malgorzata, Bordogna, Walter, Morcos, Peter N., Smoljanovic, Vlatka, Shaw, Alice T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for Cancer Research 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9365376/
https://www.ncbi.nlm.nih.gov/pubmed/35275991
http://dx.doi.org/10.1158/1078-0432.CCR-21-2840
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author Dziadziuszko, Rafal
Peters, Solange
Mok, Tony
Camidge, D. Ross
Gadgeel, Shirish M.
Ou, Sai-Hong Ignatius
Konopa, Krzysztof
Noé, Johannes
Nowicka, Malgorzata
Bordogna, Walter
Morcos, Peter N.
Smoljanovic, Vlatka
Shaw, Alice T.
author_facet Dziadziuszko, Rafal
Peters, Solange
Mok, Tony
Camidge, D. Ross
Gadgeel, Shirish M.
Ou, Sai-Hong Ignatius
Konopa, Krzysztof
Noé, Johannes
Nowicka, Malgorzata
Bordogna, Walter
Morcos, Peter N.
Smoljanovic, Vlatka
Shaw, Alice T.
author_sort Dziadziuszko, Rafal
collection PubMed
description PURPOSE: We retrospectively assessed prognostic value of circulating cell-free DNA (cfDNA) using data from the phase III ALEX study in treatment-naïve, advanced ALK+ non–small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomized to receive twice-daily alectinib 600 mg (n = 152) or crizotinib 250 mg (n = 151). cfDNA was quantified from baseline plasma samples, with patients stratified into ≤median and >median cfDNA biomarker-evaluable populations (BEP). Effect of cfDNA concentration on outcomes was analyzed using a Cox regression model with treatment group as covariate, and in multivariate analyses. RESULTS: Median cfDNA concentration in the BEP was 11.53 ng/mL (n = 276). A positive correlation was found between cfDNA concentration and number of lesions, organ lesion sites, and tumor size (sum of longest diameter; all P < 0.0001). In both treatment arms, patients in the >median BEP were more likely to experience disease progression than the ≤median BEP [alectinib adjusted HR = 2.04; 95% confidence interval (CI), 1.07–3.89; P = 0.0305 and crizotinib adjusted HR = 1.83; 95% CI, 1.11–3.00, P = 0.0169]. Median progression-free survival was longer with alectinib than crizotinib in both ≤median and >median BEPs (P < 0.0001). Overall survival data remain immature; survival probability was lower in the >median versus ≤median BEP in both treatment arms (alectinib HR = 2.52; 95% CI, 1.08–5.88; P = 0.0333 and crizotinib HR = 2.63; 95% CI, 1.27–5.47; P = 0.0096). CONCLUSIONS: These data suggest that plasma cfDNA concentration may have prognostic value in advanced ALK+ NSCLC. Prospectively designed studies are warranted to investigate this finding.
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spelling pubmed-93653762023-01-05 Circulating Cell-free DNA as a Prognostic Biomarker in Patients with Advanced ALK+ Non–small Cell Lung Cancer in the Global Phase III ALEX Trial Dziadziuszko, Rafal Peters, Solange Mok, Tony Camidge, D. Ross Gadgeel, Shirish M. Ou, Sai-Hong Ignatius Konopa, Krzysztof Noé, Johannes Nowicka, Malgorzata Bordogna, Walter Morcos, Peter N. Smoljanovic, Vlatka Shaw, Alice T. Clin Cancer Res Clinical Trials: Targeted Therapy PURPOSE: We retrospectively assessed prognostic value of circulating cell-free DNA (cfDNA) using data from the phase III ALEX study in treatment-naïve, advanced ALK+ non–small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients were randomized to receive twice-daily alectinib 600 mg (n = 152) or crizotinib 250 mg (n = 151). cfDNA was quantified from baseline plasma samples, with patients stratified into ≤median and >median cfDNA biomarker-evaluable populations (BEP). Effect of cfDNA concentration on outcomes was analyzed using a Cox regression model with treatment group as covariate, and in multivariate analyses. RESULTS: Median cfDNA concentration in the BEP was 11.53 ng/mL (n = 276). A positive correlation was found between cfDNA concentration and number of lesions, organ lesion sites, and tumor size (sum of longest diameter; all P < 0.0001). In both treatment arms, patients in the >median BEP were more likely to experience disease progression than the ≤median BEP [alectinib adjusted HR = 2.04; 95% confidence interval (CI), 1.07–3.89; P = 0.0305 and crizotinib adjusted HR = 1.83; 95% CI, 1.11–3.00, P = 0.0169]. Median progression-free survival was longer with alectinib than crizotinib in both ≤median and >median BEPs (P < 0.0001). Overall survival data remain immature; survival probability was lower in the >median versus ≤median BEP in both treatment arms (alectinib HR = 2.52; 95% CI, 1.08–5.88; P = 0.0333 and crizotinib HR = 2.63; 95% CI, 1.27–5.47; P = 0.0096). CONCLUSIONS: These data suggest that plasma cfDNA concentration may have prognostic value in advanced ALK+ NSCLC. Prospectively designed studies are warranted to investigate this finding. American Association for Cancer Research 2022-05-02 2022-02-23 /pmc/articles/PMC9365376/ /pubmed/35275991 http://dx.doi.org/10.1158/1078-0432.CCR-21-2840 Text en ©2022 The Authors; Published by the American Association for Cancer Research https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license.
spellingShingle Clinical Trials: Targeted Therapy
Dziadziuszko, Rafal
Peters, Solange
Mok, Tony
Camidge, D. Ross
Gadgeel, Shirish M.
Ou, Sai-Hong Ignatius
Konopa, Krzysztof
Noé, Johannes
Nowicka, Malgorzata
Bordogna, Walter
Morcos, Peter N.
Smoljanovic, Vlatka
Shaw, Alice T.
Circulating Cell-free DNA as a Prognostic Biomarker in Patients with Advanced ALK+ Non–small Cell Lung Cancer in the Global Phase III ALEX Trial
title Circulating Cell-free DNA as a Prognostic Biomarker in Patients with Advanced ALK+ Non–small Cell Lung Cancer in the Global Phase III ALEX Trial
title_full Circulating Cell-free DNA as a Prognostic Biomarker in Patients with Advanced ALK+ Non–small Cell Lung Cancer in the Global Phase III ALEX Trial
title_fullStr Circulating Cell-free DNA as a Prognostic Biomarker in Patients with Advanced ALK+ Non–small Cell Lung Cancer in the Global Phase III ALEX Trial
title_full_unstemmed Circulating Cell-free DNA as a Prognostic Biomarker in Patients with Advanced ALK+ Non–small Cell Lung Cancer in the Global Phase III ALEX Trial
title_short Circulating Cell-free DNA as a Prognostic Biomarker in Patients with Advanced ALK+ Non–small Cell Lung Cancer in the Global Phase III ALEX Trial
title_sort circulating cell-free dna as a prognostic biomarker in patients with advanced alk+ non–small cell lung cancer in the global phase iii alex trial
topic Clinical Trials: Targeted Therapy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9365376/
https://www.ncbi.nlm.nih.gov/pubmed/35275991
http://dx.doi.org/10.1158/1078-0432.CCR-21-2840
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