Effect of Osimertinib on CTCs and ctDNA in EGFR Mutant Non-Small Cell Lung Cancer Patients: The Prognostic Relevance of Liquid Biopsy.

Autor: Kallergi G; Department of Biology, Division of Genetics, Cell and Developmental Biology, University of Patras, 26500 Patras, Greece., Kontopodis E; Department of Medical Oncology, 'Venizelio-Pananio' General Hospital of Heraklion, 71500 Heraklion, Greece., Ntzifa A; Analysis of Circulating Tumor Cells Lab, Department of Chemistry, University of Athens, 15772 Athens, Greece.; Lab of Analytical Chemistry, Department of Chemistry, University of Athens, 15772 Athens, Greece., Jordana-Ariza N; Laboratory of Oncology, Pangaea Oncology, Quiron Dexeus University Hospital, 08028 Barcelona, Spain., Karachaliou N; Laboratory of Oncology, Pangaea Oncology, Quiron Dexeus University Hospital, 08028 Barcelona, Spain., Pantazaka E; Department of Biology, Division of Genetics, Cell and Developmental Biology, University of Patras, 26500 Patras, Greece., Charalambous HA; Oncology Center of Bank of Cyprus, Department of Medical Oncology, Nicosia 2012, Cyprus., Psyrri A; Medical Oncology Unit, 2nd Department of Internal Medicine, 'ATTIKON' General Hospital of Athens, 12462 Athens, Greece., Tsaroucha E; 7th Department of Pulmonary Diseases, 'SOTIRIA' General Hospital of Athens, 11527 Athens, Greece., Boukovinas I; Department of Medical Oncology, BIOCLINIKI Hospital, 11524 Thessaloniki, Greece., Koumarianou A; Hematology-Oncology Unit, Fourth Department of Internal Medicine, Attikon Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece., Hatzidaki D; Hellenic Oncology Research Group (HORG), 1st Department of Medical Oncology, Metropolitan General Hospital, 15562 Athens, Greece., Lianidou E; Analysis of Circulating Tumor Cells Lab, Department of Chemistry, University of Athens, 15772 Athens, Greece.; Lab of Analytical Chemistry, Department of Chemistry, University of Athens, 15772 Athens, Greece., Georgoulias V; Hellenic Oncology Research Group (HORG), 1st Department of Medical Oncology, Metropolitan General Hospital, 15562 Athens, Greece., Rosell R; Laboratory of Oncology, Pangaea Oncology, Quiron Dexeus University Hospital, 08028 Barcelona, Spain., Kotsakis A; Department of Medical Oncology, University General Hospital of Larissa, Mezourlo, 41500 Larissa, Greece.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2022 Mar 19; Vol. 14 (6). Date of Electronic Publication: 2022 Mar 19.
DOI: 10.3390/cancers14061574
Abstrakt: Introduction: Liquid biopsy is a useful tool for monitoring treatment outcome in solid tumors, including lung cancer. The relevance of monitoring CTCs and plasma ctDNA as predictors of clinical outcome was assessed in EGFR-mutant NSCLC patients treated with osimertinib.
Methods: Forty-seven EGFR-mutant NSCLC patients who had progressed on prior first- or second-generation EGFR inhibitors were enrolled in the study and treated with osimertinib, irrespective of the presence of the T790M mutation in the primary tumor or the plasma. Peripheral blood was collected at baseline ( n = 47), post-Cycle 1 ( n = 47), and at the end of treatment (EOT; n = 39). CTCs were evaluated in 32 patients at the same time points ( n = 32, n = 27, and n = 21, respectively) and phenotypic characterization was performed using triple immunofluorescence staining (CK/VIM/CD45).
Results: Osimertinib resulted in an ORR of 34% (2 CR) and a DCR of 76.6%. The median PFS and OS values were 7.5 (range, 0.8-52.8) and 15.1 (range, 2.1-52.8) months, respectively. ctDNA was detected in 61.7%, 27.7%, and 61.5% of patients at baseline, post-Cycle 1, and EOT, respectively. CTCs (CK+/CD45-) were detected in 68.8%, 48.1%, and 61.9% of patients at the three time points, respectively. CTCs expressing both epithelial and mesenchymal markers (CK+/VIM+/CD45-) were detected in 56.3% and 29.6% of patients at baseline and post-Cycle 1, respectively. The detection of ctDNA at baseline and post-Cycle 1 was associated with shorter PFS and OS, whereas the ctDNA clearance post-Cycle 1 resulted in a significantly longer PFS and OS. Multivariate analysis revealed that male sex and the detection of ctDNA at baseline were independent predictors of shorter PFS (HR: 2.6, 95% C.I.: 1.2-5.5, p = 0.015 and HR: 3.0, 95% C.I.: 1.3-6.9; p = 0.009, respectively).
Conclusions: The decrease in both CTCs and ctDNA occurring early during osimertinib treatment is predictive of better outcome, implying that liquid biopsy monitoring may be a valuable tool for the assessment of treatment efficacy.
Databáze: MEDLINE
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