Dr. Leal on the Evolution of Treatment in EGFR Exon 20 Insertion+ NSCLC

Ticiana Leal, MD, associate professor, director, Thoracic Medical Oncology Program, Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, discusses the evolution of treatment in EGFR exon 20 insertion–positive non–small cell lung cancer (NSCLC).

Historically, patients with advanced NSCLC harboring EGFR exon 20 insertions did not have available targeted treatment options, Leal explains. These patients account for approximately 12% of all patients with advanced NSCLC and are traditionally resistant to the EGFR TKIs that are used in patients with sensitizing EGFR mutations. Therefore, this disease subgroup was associated with poor prognosis, Leal adds. The median progression-free survival with EGFR TKIs, such as gefitinib (Iressa), erlotinib (Tarceva), and afatinib (Gilotrif), was less than 3 months for patients with EGFR exon 20 insertion–positive NSCLC.

The frontline standard of care for this patient population remains platinum-based chemotherapy with or without bevacizumab (Avastin), Leal says. Although immunotherapy has been transformative for many populations with lung cancer, data suggest that patients with EGFR exon 20 insertions do not derive equivalent benefit from immunotherapy. Therefore, patients had limited treatment options available when they progressed beyond frontline chemotherapy, which most patients do within 6 months.

The FDA approvals of amivantamab-vmjw (Rybrevant) and mobocertinib (Exkivity) have changed the second-line treatment for patients with advanced NSCLC who harbor EGFR exon 20 insertions, Leal concludes.