Introduction: We retrospectively assessed prognostic value of circulating cell-free DNA (cfDNA) using data from the phase III ALEX study in treatment-naïve, advanced <em>ALK</em>+ NSCLC. Methods: Patients were randomized to receive twice-daily alectinib 600 mg (<em>n</em> = 152) or crizotinib 250 mg (<em>n</em> = 151). cfDNA was quantified from baseline plasma samples, with patients stratified into {less than or equal to}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 (<em>n</em> = 276). A positive correlation was found between cfDNA concentration and number of lesions, organ lesion sites, and tumor size (sum of longest diameter; all <em>p</em><0.0001). In both treatment arms, patients in the >median BEP were more likely to experience disease progression than the {less than or equal to}median BEP (alectinib adjusted hazard ratio [HR] 2.04 [95% confidence interval (CI): 1.07-3.89], <em>p</em>=0.0305; crizotinib adjusted HR 1.83 [95% CI: 1.11-3.00], <em>p</em>=0.0169). Median progression-free survival was longer with alectinib than crizotinib in both {less than or equal to}median and >median BEPs (<em>p</em><0.0001). Overall survival data remain immature; survival probability was lower in the >median versus {less than or equal to}median BEP in both treatment arms (alectinib HR 2.52 [95% CI: 1.08-5.88], <em>p</em>=0.0333; crizotinib HR 2.63 [95% CI: 1.27-5.47], <em>p</em>=0.0096). Conclusion: These data suggest that plasma cfDNA concentration may have prognostic value in advanced <em>ALK</em>+ NSCLC. Prospectively designed studies are warranted to investigate this finding. READ ARTICLE
Clinical Cancer Research DOI:10.1158/1078-0432.CCR-21-2840
Authors: Rafal Dziadziuszko, Solange Peters, Tony Mok, D. Ross. Camidge, Shirish M. Gadgeel, Sai-Hong Ignatius. Ou, Krzysztof Konopa, Johannes Noé, Malgorzata Nowicka, Walter Bordogna, Peter N. Morcos, Vlatka Smoljanovic, Alice T. Shaw
