Dr. Clarke on Available EGFR TKIs in Frontline Treatment of EGFR+ NSCLC

Jeffrey M. Clarke, MD, assistant professor of medicine, Duke Cancer Institute, discusses the available EGFR TKIs in the frontline setting for the treatment of patients with EGFR-positive non—small cell lung cancer (NSCLC).

Currently there are 5 FDA-approved TKIs indicated for frontline treatment of patients with EGFR-positive NSCLC; these include erlotinib (Tarceva), gefitinib (Iressa), afatinib (Gilotrif), dacomitinib (Vizimpro), and osimertinib (Tagrisso).

Most notably were the results of the phase III FLAURA study, which prompted the FDA approval of osimertinib in April 2018. In the trial, patients were randomized to receive either osimertinib, gefitinib, or erlotinib. Investigators reported a significant improvement in progression-free survival (PFS) in patients who received osimertinib; overall survival (OS) data are still maturing. Overall, the therapy was well tolerated with low incidences of rash. The study was practice-changing, says Clarke.

In 2018, the FDA also approved dacomitinib, which shows higher rates of grade 3/4 diarrhea and rash compared with gefitinib. However, an improvement in PFS as well as OS has been seen with dacomitinib. At this point, most [healthcare providers] feel that osimertinib remains the preferred frontline therapy based on tolerability and PFS benefit, concludes Clarke.