Executive Summary - EGFR Exon 20ins EQA 2021 DACH Region

EGFR exon 20 insertions are rare somatic alterations in non-small cell lung cancer (NSCLC). They occur with a frequency of 4 % to 12 % of all EGFR alterations and show a large heterogeneity of inserted or duplicated amino acids. EGFR exon 20 insertions lead to therapy failure to first-, second- and third-generation tyrosine kinase inhibitors (TKI), but recently new therapy approaches such as with the bispecific antibody amivantamab and the TKI mobocertinib showed promising results in clinical trials. This led to FDA approval for both drugs and since December 9th, amivantamab has also been approved by EMA.
The aim of the proficiency test "EGFR exon 20 insertions" is the quality control of validated, correctly performed, and reproducible EGFR exon 20 testing in the participating institutes.
In 2021 a total number of 67 of pathologies/labs from Germany, Austria and Switzerland participated in this proficiency test conducted by QuIP.
The EGFR exon 20 insertion proficiency test is comprised of two method segments (tissue testing and liquid biopsy testing). Different sample types are used for each of the methods, yielding a total of 10 different cases which are to be evaluated per method.
Most participants passed the tissue part of the proficiency test and most of the participants used parallel sequencing for mutation detection followed by allele-specific PCR with different systems and Sanger sequencing.
Especially use of PCR-based methods led to false negative results as some of the rarer EGFR Exon20ins mutations were not covered by certain assays.
Less participants than in the tissue part passed the liquid biopsy part of the proficiency test. Again, parallel sequencing was most often used as detection method.
This proficiency test shows that a broad range of EGFR exon 20 mutations can be reliably detected in routine tissue and liquid biopsy samples if the test is suitable and validated.