Types of EGFR Therapy in NSCLC

For High-Definition, Click

Each generation of EGFR inhibitor has unique attributes and potency, which defines these classifications, notes Heather A. Wakelee, MD. The first-generation EGFR TKIs target wild-type polymorphisms as well as sensitive mutants but not T790M, an acquired resistance mutation. These agents include erlotinib and gefitinib. The second-generation agents, such as afatinib, have some activity against T790M, but are more potent against standard sensitizing mutations. The third-generation agents have increased sensitivity to T790M and standard EGFR mutations, but not wild-type targets.

At this time, the FDA has not yet approved a third-generation agent, notes Wakelee. The experimental agents AZD9291 and rociletinib have shown significant activity in patients with non-small cell lung cancer (NSCLC) with T790M resistance mutations. Based on evidence from early phase clinical trials, both third-generation agents have received breakthrough therapy designations from the FDA.

For both agents, the overall response rates in patients with NSCLC who harbor an EGFR T790M mutation ranges from 50% to 60%, and with T790M-negative tumors, from 20% to 30%. Anne S. Tsao, MD, notes that because these third-generation inhibitors are more targeted, there is less toxicity, including the diarrhea and rash that is common with the earlier-generation TKIs.

Related Videos
Yasushi Goto, MD
In this first episode of OncChats: Examining LIFU–Aided Liquid Biopsy in Glioblastoma, Manmeet Singh Ahluwalia, MD, and Michael W. McDermott, MD, explain how low-intensity focused ultrasound works and the rationale for examining its use in cancer and other conditions.
Roy S. Herbst, MD, PhD
Experts on lung cancer
Stephen V. Liu, MD
Edgardo S. Santos, MD, FACP
Edgardo S. Santos, MD, FACP
Related Content