Circulating Tumor DNA Analysis to Assess Risk of Progression after Long-term Response to PD-(L)1 Blockade in NSCLC.

Autor:	Hellmann MD; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. diehn@stanford.edu arasha@stanford.edu hellmanm@mskcc.org.; Weill Cornell School of Medicine, New York, New York.; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York.; Parker Center for Cancer Immunotherapy, San Francisco, California., Nabet BY; Department of Radiation Oncology, Stanford University, Stanford, California.; Stanford Cancer Institute, Stanford University, Stanford, California., Rizvi H; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York., Chaudhuri AA; Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri., Wells DK; Parker Center for Cancer Immunotherapy, San Francisco, California., Dunphy MPS; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York., Chabon JJ; Department of Radiation Oncology, Stanford University, Stanford, California.; Stanford Cancer Institute, Stanford University, Stanford, California., Liu CL; Stanford Cancer Institute, Stanford University, Stanford, California.; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California., Hui AB; Department of Radiation Oncology, Stanford University, Stanford, California.; Stanford Cancer Institute, Stanford University, Stanford, California., Arbour KC; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell School of Medicine, New York, New York.; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York., Luo J; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Preeshagul IR; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York., Moding EJ; Department of Radiation Oncology, Stanford University, Stanford, California.; Stanford Cancer Institute, Stanford University, Stanford, California., Almanza D; Department of Radiation Oncology, Stanford University, Stanford, California.; Stanford Cancer Institute, Stanford University, Stanford, California., Bonilla RF; Department of Radiation Oncology, Stanford University, Stanford, California., Sauter JL; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York., Choi H; Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, New York., Tenet M; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York., Abu-Akeel M; Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, New York., Plodkowski AJ; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York., Perez Johnston R; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York., Yoo CH; Department of Radiation Oncology, Stanford University, Stanford, California., Ko RB; Department of Radiation Oncology, Stanford University, Stanford, California., Stehr H; Department of Pathology, Stanford University, Stanford, California., Gojenola L; Department of Pathology, Stanford University, Stanford, California., Wakelee HA; Stanford Cancer Institute, Stanford University, Stanford, California.; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California., Padda SK; Stanford Cancer Institute, Stanford University, Stanford, California.; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California., Neal JW; Stanford Cancer Institute, Stanford University, Stanford, California.; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California., Chaft JE; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell School of Medicine, New York, New York.; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York., Kris MG; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell School of Medicine, New York, New York.; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York., Rudin CM; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell School of Medicine, New York, New York.; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York., Merghoub T; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell School of Medicine, New York, New York.; Parker Center for Cancer Immunotherapy, San Francisco, California.; Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, New York., Li BT; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.; Weill Cornell School of Medicine, New York, New York.; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York., Alizadeh AA; Stanford Cancer Institute, Stanford University, Stanford, California. diehn@stanford.edu arasha@stanford.edu hellmanm@mskcc.org.; Division of Oncology, Department of Medicine, Stanford Cancer Institute, Stanford University, Stanford, California., Diehn M; Department of Radiation Oncology, Stanford University, Stanford, California. diehn@stanford.edu arasha@stanford.edu hellmanm@mskcc.org.; Stanford Cancer Institute, Stanford University, Stanford, California.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Jun 15; Vol. 26 (12), pp. 2849-2858. Date of Electronic Publication: 2020 Feb 11.
DOI:	10.1158/1078-0432.CCR-19-3418
Abstrakt:	Purpose: Treatment with PD-(L)1 blockade can produce remarkably durable responses in patients with non-small cell lung cancer (NSCLC). However, a significant fraction of long-term responders ultimately progress and predictors of late progression are unknown. We hypothesized that circulating tumor DNA (ctDNA) analysis of long-term responders to PD-(L)1 blockade may differentiate those who will achieve ongoing benefit from those at risk of eventual progression. Experimental Design: In patients with advanced NSCLC achieving long-term benefit from PD-(L)1 blockade (progression-free survival ≥ 12 months), plasma was collected at a surveillance timepoint late during/after treatment to interrogate ctDNA by Cancer Personalized Profiling by Deep Sequencing. Tumor tissue was available for 24 patients and was profiled by whole-exome sequencing ( n = 18) or by targeted sequencing ( n = 6). Results: Thirty-one patients with NSCLC with long-term benefit to PD-(L)1 blockade were identified, and ctDNA was analyzed in surveillance blood samples collected at a median of 26.7 months after initiation of therapy. Nine patients also had baseline plasma samples available, and all had detectable ctDNA prior to therapy initiation. At the surveillance timepoint, 27 patients had undetectable ctDNA and 25 (93%) have remained progression-free; in contrast, all 4 patients with detectable ctDNA eventually progressed [Fisher P < 0.0001; positive predictive value = 1, 95% confidence interval (CI), 0.51-1; negative predictive value = 0.93 (95% CI, 0.80-0.99)]. Conclusions: ctDNA analysis can noninvasively identify minimal residual disease in patients with long-term responses to PD-(L)1 blockade and predict the risk of eventual progression. If validated, ctDNA surveillance may facilitate personalization of the duration of immune checkpoint blockade and enable early intervention in patients at high risk for progression. (©2020 American Association for Cancer Research.)
Databáze:	MEDLINE
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