Biology and Subtypes of EGFR Exon 20 Insertions

Lyudmila Bazhenova, MD, of UC San Diego Moores Cancer Center, opens this OncLive Insights discussion on EGFR exon 20 insertion–mutated non–small cell lung cancer with Pasi A. Jänne, MD, PhD, of Dana-Farber Cancer Institute. Dr Jänne explains that exon 20 insertions are small insertions or duplications that make up about 8% to 10% of EGFR mutations, less common than exon 19 deletions or L858R mutations. They have historically carried a poorer prognosis and a poorer response to earlier EGFR inhibitors, partly because insertions block drugs from entering the adenosine triphosphate (ATP) binding pocket. Insertions are grouped by location into helical, near-loop, and far-loop subtypes. Dr Bazhenova still looks up where a given insertion falls and does not choose treatment by location. Dr Jänne calls location-based selection a research question rather than a practice question, since the agents tested show fairly similar activity across subtypes and not all are available.