Molecular Testing and Reporting of Exon 20 Insertions

Pasi A. Jänne, MD, PhD, of Dana-Farber Cancer Institute, notes that some patients with EGFR exon 20 insertion–mutated non–small cell lung cancer receive EGFR inhibitors never developed for this mutation, including osimertinib. Lyudmila Bazhenova, MD, of UC San Diego Moores Cancer Center, traces this to reports that do not always name the alteration, and asks laboratories to label exon 20 insertions and list amivantamab plus chemotherapy rather than osimertinib, gefitinib, or afatinib. Dr Jänne uses tissue-based next-generation sequencing (NGS), because older polymerase chain reaction (PCR) assays targeting specific variants missed many of the roughly 100 exon 20 variants, and uses liquid biopsy when tissue is unavailable. Dr Bazhenova sends liquid and tissue testing together because commercial NGS takes about 2 to 2.5 weeks. She starts targeted therapy on a positive liquid result and waits for tissue when liquid testing is negative, which she says happens in about 30% of patients.