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19.02.2021 | Original Research Article Open Access

Clinical Value of EGFR Copy Number Gain Determined by Amplicon-Based Targeted Next Generation Sequencing in Patients with EGFR-Mutated NSCLC

Targeted Oncology
Jiacong Wei, Pei Meng, Miente Martijn Terpstra, Anke van Rijk, Menno Tamminga, Frank Scherpen, Arja ter Elst, Mohamed Z. Alimohamed, Lennart F. Johansson, Jos Stigt, Rolof P. G. Gijtenbeek, John van Putten, T. Jeroen N. Hiltermann, Harry J. M. Groen, Klaas Kok, Anthonie J. van der Wekken, Anke van den Berg
Wichtige Hinweise

Supplementary Information

The online version contains supplementary material available at https://​doi.​org/​10.​1007/​s11523-021-00798-2.
Jiacong Wei and Pei Meng contributed equally to the article.



The clinical relevance of epidermal growth factor receptor (EGFR) copy number gain in patients with EGFR mutated advanced non-small cell lung cancer on first-line tyrosine kinase inhibitor treatment has not been fully elucidated.


We aimed to estimate EGFR copy number gain using amplicon-based next generation sequencing data and explored its prognostic value.

Patients and Methods

Next generation sequencing data were obtained for 1566 patients with non-small cell lung cancer. EGFR copy number gain was defined based on an increase in EGFR read counts relative to internal reference amplicons and normal controls in combination with a modified z-score ≥ 3.5. Clinical follow-up data were available for 60 patients treated with first-line EGFR-tyrosine kinase inhibitors.


Specificity and sensitivity of next generation sequencing-based EGFR copy number estimations were above 90%. EGFR copy number gain was observed in 27.9% of EGFR mutant cases and in 7.4% of EGFR wild-type cases. EGFR gain was not associated with progression-free survival but showed a significant effect on overall survival with an adjusted hazard ratio of 3.14 (95% confidence interval 1.46–6.78, p = 0.003). Besides EGFR copy number gain, osimertinib in second or subsequent lines of treatment and the presence of T790M at relapse revealed significant effects in a multivariate analysis with adjusted hazard ratio of 0.43 (95% confidence interval 0.20–0.91, p = 0.028) and 0.24 (95% confidence interval 0.1–0.59, p = 0.001), respectively.


Pre-treatment EGFR copy number gain determined by amplicon-based next generation sequencing data predicts worse overall survival in EGFR-mutated patients treated with first-line EGFR-tyrosine kinase inhibitors. T790M at relapse and subsequent treatment with osimertinib predict longer overall survival.

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