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.
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Data availability
The data of this study are available from the corresponding author upon reasonable request.
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Remy Verheijen is an employee and shareholder of AstraZeneca and Johnson & Johnson. All other authors declare they have no conflicts to disclose.
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For this retrospective observational study, no informed consent was required in accordance with code of conduct for responsible use of human tissue and medical research [18].
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For this retrospective observational study, no informed consent was required in accordance with code of conduct for responsible use of human tissue and medical research [18].
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Verheijen, R.B., van Duijl, T.T., van den Heuvel, M.M. et al. Monitoring of EGFR mutations in circulating tumor DNA of non-small cell lung cancer patients treated with EGFR inhibitors. Cancer Chemother Pharmacol 87, 269–276 (2021). https://doi.org/10.1007/s00280-021-04230-4
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DOI: https://doi.org/10.1007/s00280-021-04230-4