Third-Generation EGFR Inhibitors in NSCLC

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Third-generation EGFR TKIs, such as rociletinib and AZD9291, are better tolerated than first-generation agents from this class, states Heather A. Wakelee, MD. In clinical studies, these agents have demonstrated promising response rates for patients with an acquired T790M resistance mutation. The overall response rate for these agents in the second-line setting following progression on a first-generation TKI is near 60%.

Adverse events associated with AZD9291 include minor rash and diarrhea. Additionally, lung effects that were observed with the first- and second-generation TKIs are present with the third-generation TKIs, but to a much lesser degree. Rociletinib may result in hyperglycemia, an event that is easily managed.

Both of these therapies are being evaluated as first-line therapies compared with standard of care first-generation EGFR TKIs. In addition to these novel agents, potential combination strategies could play a role in the future treatment of patients, notes Roy S. Herbst, MD, PhD. Clinical studies are assessing combinations of ALK or EGFR targeted therapies with immune checkpoint inhibition in NSCLC. These approaches could offer a new option for patients with this disease, Herbst notes.