Eva Boysen Fynboe Ebert1, Tine McCulloch2, Karin Holmskov Hansen3, Hanne Linnet4, Boe Sorensen5, Peter Meldgaard6. 1. Department of Oncology, Aarhus University Hospital, Palle Juul-Jensens Blvd. 99, 8200 Aarhus, Denmark. Electronic address: evhase@rm.dk. 2. Department of Oncology, Aalborg University Hospital, Hobrovej 18-22, 9100 Aalborg, Denmark. Electronic address: tine.mcculloch@rn.dk. 3. Department of Oncology, Odense University Hospital, J.B. Winsløws Vej 4, 5000 Odense, Denmark. Electronic address: karin.holmskov@rsyd.dk. 4. Department of Oncology, Herning Regional Hospital, Gl. Landevej 61, 7400 Herning, Denmark. Electronic address: Hannsind@rm.dk. 5. Department of Biochemistry, Aarhus University Hospital, Palle Juul-Jensens Blvd. 99, 8200 Aarhus, Denmark. Electronic address: boesoere@rm.dk. 6. Department of Oncology, Aarhus University Hospital, Palle Juul-Jensens Blvd. 99, 8200 Aarhus, Denmark. Electronic address: petemeld@rm.dk.
Abstract
OBJECTIVES: Epidermal growth factor receptor (EGFR) mutations confer sensitivity to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). However, a subset of patients has limited or no response. We investigated the initial dynamics of EGFR mutations detected in circulating tumour DNA (ctDNA) during treatment as a predictive marker of outcome. METHODS: A total of 225 patients with advanced EGFR mutated NSCLC were included for consecutive blood sampling in this prospective multicentre study. Out of these, 146 patients received first line TKI and had a baseline blood sample available for EGFR mutation testing with the Cobas® EGFR mutation test V2. For examinations on clearing and clinical outcome, 98 patients who had detectable ctDNA at baseline and at least one follow-up blood sample were included. RESULTS: For patients with EGFR mutations present in plasma at baseline, clearing of mutations from the blood during first line TKI served as a positive predictor for objective response rate (p = 0.0008), progression-free survival (PFS) (p < 0.0001) and overall survival (OS) (p < 0.0001). This was seen both for patients who cleared the ctDNA within the first 7 weeks of treatment and patients who cleared the ctDNA at a slower pace. Baseline mutation presence was a negative predictor for PFS (p = 0.0069) and OS (p = 0.0340). CONCLUSION: The current study is the first to confirm, in a sizeable Caucasian cohort, that clearing of EGFR mutations predict outcome to first line TKI in patients with EGFR mutated NSCLC.
OBJECTIVES:Epidermal growth factor receptor (EGFR) mutations confer sensitivity to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). However, a subset of patients has limited or no response. We investigated the initial dynamics of EGFR mutations detected in circulating tumour DNA (ctDNA) during treatment as a predictive marker of outcome. METHODS: A total of 225 patients with advanced EGFR mutated NSCLC were included for consecutive blood sampling in this prospective multicentre study. Out of these, 146 patients received first line TKI and had a baseline blood sample available for EGFR mutation testing with the Cobas® EGFR mutation test V2. For examinations on clearing and clinical outcome, 98 patients who had detectable ctDNA at baseline and at least one follow-up blood sample were included. RESULTS: For patients with EGFR mutations present in plasma at baseline, clearing of mutations from the blood during first line TKI served as a positive predictor for objective response rate (p = 0.0008), progression-free survival (PFS) (p < 0.0001) and overall survival (OS) (p < 0.0001). This was seen both for patients who cleared the ctDNA within the first 7 weeks of treatment and patients who cleared the ctDNA at a slower pace. Baseline mutation presence was a negative predictor for PFS (p = 0.0069) and OS (p = 0.0340). CONCLUSION: The current study is the first to confirm, in a sizeable Caucasian cohort, that clearing of EGFR mutations predict outcome to first line TKI in patients with EGFR mutated NSCLC.
Authors: Ekaterina S Kuligina; Fedor V Moiseyenko; Albina S Zhabina; Sergey A Belukhin; Tatiana A Laidus; Aleksandr S Martianov; Kirill A Zagorodnev; Tatyana N Sokolova; Svetlana A Chuinyshena; Maxim M Kholmatov; Elizaveta V Artemieva; Ekaterina O Stepanova; Tatiana N Shuginova; Nikita M Volkov; Grigoriy A Yanus; Evgeny N Imyanitov Journal: Int J Clin Oncol Date: 2022-02-16 Impact factor: 3.850