EGFR Exon 20 Insertion NSCLC: Prevalence, Testing, and Standard of Care

Welcome back to another AJMC Post-Conference Perspectives series. In "EGFR Exon 20 Insertion NSCLC: Prevalence, Testing, and Standard of Care," Helena Yu, MD, of MSK Cancer Center, opens the series by defining this uncommon molecular subgroup and how it is identified.

Dr. Yu begins by noting that mutation testing is now routine for every patient diagnosed with non-small cell lung cancer. EGFR mutations as a group account for roughly 20% of these diagnoses. That group spans common sensitizing mutations, atypical or uncommon mutations, and exon 20 insertions. Exon 20 insertions make up about 10% of EGFR-mutant cases, or roughly 2% of all US patients with non-small cell lung cancer. She adds that EGFR mutation incidence varies widely by region, reaching half or more of patients in parts of Asia.

Turning to diagnosis, Dr. Yu describes using a large next-generation sequencing panel that multiplexes all targetable alterations in a single assay. Tissue-based sequencing is most common at initial diagnosis, because the biopsy or surgical specimen can also support mutation testing. Liquid biopsy, which detects circulating tumor DNA in plasma, offers a second route. She views the two approaches as complementary and largely overlapping. Tissue remains the historical gold standard, yet each test can catch alterations the other misses. When the first test finds no driver, she recommends sending the other.

Dr. Yu then traces how first-line care has changed over the last several years, and she expects further change within a year or two. Patients were once treated with chemotherapy because no approved first-line targeted option existed. The PAPILLON study changed that by adding amivantamab, an EGFR-MET bispecific antibody first approved after chemotherapy, to first-line chemotherapy. The combination proved superior to chemotherapy alone in both progression-free and overall survival. She uses it for most of her patients, although the two agents carry different toxicity profiles. For patients unlikely to tolerate both, she considers giving one agent first and sequencing the other later.

Our next episode, "Selecting First-Line Therapy in EGFR Exon 20 NSCLC: Toxicity and Monitoring," follows Dr. Yu as she weighs efficacy against patient factors and explains how she anticipates and manages treatment-related toxicities.