R B Verheijen1, T T van Duijl2, M M van den Heuvel3,4, D Vessies5, M Muller4, J H Beijnen2,6, J M Janssen2, J H M Schellens6,7, N Steeghs7, D van den Broek5, A D R Huitema2,8. 1. Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands. r.verheijen@nki.nl. 2. Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek, Louwesweg 6, 1066 EC, Amsterdam, The Netherlands. 3. Department of Respiratory Disease, Radboud University Medical Centre, Nijmegen, The Netherlands. 4. Department of Thoracic Oncology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek, Amsterdam, The Netherlands. 5. Department of Laboratory Medicine, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek, Amsterdam, The Netherlands. 6. Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. 7. Department of Medical Oncology and Clinical Pharmacology, The Netherlands Cancer Institute - Antoni Van Leeuwenhoek, Amsterdam, The Netherlands. 8. Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.
Abstract
PURPOSE: We studied EGFR mutations in circulating tumor DNA (ctDNA) and explored their role in predicting the progression-free survival (PFS) of non-small cell lung cancer (NSCLC) patients treated with erlotinib or gefitinib. METHODS: The L858R, T790M mutations and exon 19 deletions were quantified in plasma using digital droplet polymerase chain reaction (ddPCR). The dynamics of ctDNA mutations over time and relationships with PFS were explored. RESULTS: In total, 249 plasma samples (1-13 per patient) were available from 68 NSCLC patients. The T790M and L858R or exon 19 deletion were found in the ctDNA of 49 and 56% patients, respectively. The median (range) concentration in these samples were 7.3 (5.1-3688.7), 11.7 (5.1-12,393.3) and 27.9 (5.9-2896.7) copies/mL, respectively. Using local polynomial regression, the number of copies of EGFR mutations per mL increased several months prior to progression on standard response evaluation. CONCLUSION: This change was more pronounced for the driver mutations than for the resistance mutations. In conclusion, quantification of EGFR mutations in plasma ctDNA was predictive of treatment outcomes in NSCLC patients. In particular, an increase in driver mutation copy number could predict disease progression.
PURPOSE: We studied EGFR mutations in circulating tumor DNA (ctDNA) and explored their role in predicting the progression-free survival (PFS) of non-small cell lung cancer (NSCLC) patients treated with erlotinib or gefitinib. METHODS: The L858R, T790M mutations and exon 19 deletions were quantified in plasma using digital droplet polymerase chain reaction (ddPCR). The dynamics of ctDNA mutations over time and relationships with PFS were explored. RESULTS: In total, 249 plasma samples (1-13 per patient) were available from 68 NSCLCpatients. The T790M and L858R or exon 19 deletion were found in the ctDNA of 49 and 56% patients, respectively. The median (range) concentration in these samples were 7.3 (5.1-3688.7), 11.7 (5.1-12,393.3) and 27.9 (5.9-2896.7) copies/mL, respectively. Using local polynomial regression, the number of copies of EGFR mutations per mL increased several months prior to progression on standard response evaluation. CONCLUSION: This change was more pronounced for the driver mutations than for the resistance mutations. In conclusion, quantification of EGFR mutations in plasma ctDNA was predictive of treatment outcomes in NSCLCpatients. In particular, an increase in driver mutation copy number could predict disease progression.
Authors: Juliann Chmielecki; Jasmine Foo; Geoffrey R Oxnard; Katherine Hutchinson; Kadoaki Ohashi; Romel Somwar; Lu Wang; Katherine R Amato; Maria Arcila; Martin L Sos; Nicholas D Socci; Agnes Viale; Elisa de Stanchina; Michelle S Ginsberg; Roman K Thomas; Mark G Kris; Akira Inoue; Marc Ladanyi; Vincent A Miller; Franziska Michor; William Pao Journal: Sci Transl Med Date: 2011-07-06 Impact factor: 17.956
Authors: Tony S Mok; Yi-Long Wu; Myung-Ju Ahn; Marina C Garassino; Hye R Kim; Suresh S Ramalingam; Frances A Shepherd; Yong He; Hiroaki Akamatsu; Willemijn S M E Theelen; Chee K Lee; Martin Sebastian; Alison Templeton; Helen Mann; Marcelo Marotti; Serban Ghiorghiu; Vassiliki A Papadimitrakopoulou Journal: N Engl J Med Date: 2016-12-06 Impact factor: 91.245
Authors: Raees Tonse; Muni Rubens; Haley Appel; Martin C Tom; Matthew D Hall; Yazmin Odia; Michael W McDermott; Manmeet S Ahluwalia; Minesh P Mehta; Rupesh Kotecha Journal: Discov Oncol Date: 2021-11-08
Authors: Julie M Janssen; Remy B Verheijen; Tirsa T van Duijl; Lishi Lin; Michel M van den Heuvel; Jos H Beijnen; Neeltje Steeghs; Daan van den Broek; Alwin D R Huitema; Thomas P C Dorlo Journal: Clin Transl Sci Date: 2022-06-30 Impact factor: 4.438