Circulating tumor DNA analysis of EGFR-mutant non-small cell lung cancer patients receiving osimertinib following previous tyrosine kinase inhibitor treatment

Jamie J. Beagan, Sander Bach, Robert A. van Boerdonk, Erik van Dijk, Erik Thunnissen, Daan van den Broek, Janneke Weiss, Geert Kazemier, D. Michiel Pegtel, Idris Bahce, Bauke Ylstra, Daniëlle A.M. Heideman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objectives: Circulating tumor (ct)DNA analysis is rapidly gaining acceptance as a diagnostic tool to guide clinical management of advanced non-small cell lung cancer (NSCLC). Clinically-actionable EGFR mutations can be detected in ctDNA before or after first-line EGFR-Tyrosine Kinase Inhibitor (TKI) treatment, but data are limited for patients with a complex treatment history. This study aimed to explore the feasibility of ctDNA testing in a clinical setting of NSCLC patients receiving osimertinib as a second or third line EGFR-TKI. Materials and Methods: Twenty EGFR T790M-positive NSCLC patients, who had received osimertinib as a second or third line EGFR-TKI and had donated blood samples while attending routine follow-up consultations between April and November 2016, were retrospectively selected to test plasma cfDNA for tumor-guided EGFR mutations. We used EGFR mutations previously identified in tumor-tissue to retrospectively test plasma ctDNA from 20 patients who had received osimertinib as a second or third line EGFR-TKI. Both EGFR-TKI sensitising and T790 M resistance mutations were analysed by droplet digital PCR (ddPCR) in plasma taken alongside routine consultations and ctDNA detection was correlated with response under osimertinib. Follow-up solid-tissue biopsies were obtained after disease progression. Results: CtDNA was detected under osimertinib treatment in four out of the eight patients (50 %) who showed no response, two out of the seven (29 %) who showed an initial response and none of the five patients (0 %) who showed an ongoing response. The fraction of EGFR-mutant ctDNA in plasma tended to be higher in non-responders (0.1–68 %), compared to the initial responders (0.2–1.1 %). Blood samples were donated up to 34, 27 and 49 weeks after the start of osimertinib for the non-, initial and ongoing responders, respectively. Conclusions: These findings support a potential role for ctDNA analysis in response monitoring of NSCLC patients with a complex EGFR-TKI treatment history. The weak trend between ctDNA detection and disease progression warrants larger studies to further investigate potential clinical utility.

Original languageEnglish
Pages (from-to)173-180
Number of pages8
JournalLung Cancer
Volume145
DOIs
Publication statusPublished - Jul 2020

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